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Biochem. and Medical Genetics
BGEN 3020
Jason Leboe- Mcgowan

Chapter 26 Types of calcification: dystrophic and metastatic A. Dystrophic calcification: means abnormal calcification. The damaged tissue gets calcified. 1. Example: Seen in enzymatic fat necrosis (chalky white areas on x-ray are a result of dystrophic calcification). 2. Example: football player with hematoma in foot, that becomes calcified dsystrophically (Ca binds and co-produces dystrophic Ca deposits). Serum Ca is normal, but damaged tissue becomes calcified. Occurs in atheromatous plaques (causes serious tissue damage), therefore they are difficult to dissolve (need to be on the ornish diet – a vegan diet). 3. MCC aortic stenosis (MCC: congenital bicuspid aortic valve) = dystrophic calcification (also leads to a hemolytic anemia). Slide: the aorta has only 2 valves doing the job of three, and gets damaged, leading to dystrophic calcification which narrows orifice of valve, leading to aortic stenosis. B. Metastatic calcification: In cases of Hypercalcemia or hyperphosphatemia, Calcium is actually made to deposit in normal tissues, non-damaged tissues. MCC hypercalcemia (outside of hospital) = primary hyperparathyroidism MCC hypercalcemia (inside the hospital) = malignancy induced hypercalcemia. With hypercalcemia, can put Ca in NORMAL tissues; this is called metastatic calcification. In dystrophic calcification there is damaged tissue with normal serum Ca levels. Metastatic calcification is when there is high Ca or phosphorus serum levels (actually when Ca is deposited into bone, it is the phosphorus part of solubility product that drives Ca into bone). High phosphate levels (very dangerous) will take Ca and drive it into normal tissue. This is why have to put a pt with renal failure on dialysis (have high phosphorus serum levels) therefore need to dialyze the phosphate b/c the phosphate will drive Ca into normal tissue – ie heart, conduction system, renal tubules, basement membrane (nephrocalcinosis) – all lead to damage. Cell Membrane Defects A. RBC membrane defect: Spherocytosis is a defect in spectrin within RBC cell membrane; if you can’t see a central area of pallor (if you don’t see a donut) then it’s a spherocyte. Absence of spectrin with in the RBC does not allow the RBC to form a biconcave disk; it is defective, and therefore forms a sphere. B. Ubiquitin – stress protein. High ubiquitin levels are associated with high levels of stress. Some of the intermediate filaments (keratin, desmin, vimentin) are part of the superstructure of our cells (“frame of the cell”, upon which things are built). When these intermediate filaments get damaged, the ubiquitin marks then for destruction. The intermediate filaments have been tagged (ubiquinated) and marked for destruction. Some of these products have names, for example: there are open spaces within the liver tisse, these spaces are fat and they are probably due to alcohol. The ubiquinited products of the liver are called Mallory bodies. These are the result of ubiquinated filaments called keratin and these are seen in alcoholic hepatitis. Another example: Silver stain of neurofibilary tangles – Jacob crutzfelt and alzheimers dz. Tau protein is associated with neurofib tangles; this is an example of a ubiquinated neurofilament. Example: Substantia nigra in Parkinson’s Dz – include inclusions called Lewy bodies, neurotransmitter deficiency is dopamine. Lewy bodies are ubiquinated neurofilaments. Therefore, Mallory bodies, Lewy bodies, and neurofib tangles are all examples of ubiquintation. Cell Cycle- very very important: big big big time A. Different types of cells: 1. Labile cells – cell where the division is via a stem cell. Three tissues that has stem cells: bone marrow, basement membrane of skin, and the base of crypts in the intestine. These cells have the tendency of being in the cell cycle a lot. In pharm: there are cell cycle specific and cell cycle nonspecific drugs. The cells that are most affected by these drugs are the labile cells b/c they are in the cell cycle. Complications of these drugs are BM suppression, diarrhea, mucocidis, and rashes on the skin (there are stem cells in all these tissues!). 2. Stable cells – in resting phase, G ohase. Most of perenchymal organs (liver, spleen, and kidney) and smooth muscle are stable cells. Stable cells can ungo division, but most of the time they are resting, and something must stimulate them to get into the cell cycle and divide – ie a hormone or a growth factor. For example: estrogen in woman will help in the proliferative phase of the menstrual cycle. The endometrial cells are initially in the G phaseoand then the estrogen stimulated the cells to go into the the cell cycle. Therefore, they can divide, but they have to be invited by a hormone or a growth factor. 3. Permanent cells – can no longer get into the cell cycle, and have been permanently differentiated. The other types of muscle cells: striated, cardiac and neuronal cells. Only muscle that is NOT a permanent tissue = smooth muscle; hyperplasia = increase in #, while hypertrophy = increase in size. Would a permanent cell be able to under hyperplasia? NO, b/c that means more copies of it. Can it go under hypertrophy? Yes. A smooth muscle cell can undergo hyperplasia AND hypertrophy. B. Different phases of cell cycle: 1. G 1hase: The most variable phase of cell cycle is the G phase1 Compare with men
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