Lecture 15 Flashcards
(24 cards)
What do DPP-4 inhibitors do? What are the advantages and disadvantages of taking this medication to treat type II diabetes?
DPP-4 inhibitors increase your incretins (gut hormones which increase the amount of insulin and your insulin response).
Advantages: This medication is well tolerated, meaning that there are low side effects, and no hypoglycemia (low blood sugar) occurs while taking this drug.
Disadvantages: Only has a modest decrease in HbA1C (not great), has been associated with pancreas inflammation, and can also cause hives.
What do GLP-1 receptor agonists do? What are the advantages and disadvantages of taking this medication to treat type II diabetes?
GLP-1 (glucagon-like peptide-1) receptor agonists (essentially an incretin agonist) are going to activate the same receptors that GLP-1 activate. This will increase the insulin response and decrease the glucagon response.
Advantages: can lead to weight loss, does not lead to hypoglycemia, it may help protect beta cell mass, and it has a slight cardiovascular protection.
Disadvantages: can have some side effects in the gastrointestinal tract, can lead to pancreas inflammation, might cause thyroid cancer, and it is injectable.
How often do calcium and phosphorus need to be taken in? Where is calcium absorbed in our body, and what other molecule does this depend on?
They need to be taken daily. Calcium is absorbed through small intestine, which largely depends on the active form of vitamin D
What are the most abundant elements in the human body?
NOCHCaP
Nitrogen, oxygen, carbon, hydrogen, calcium, phosphorus
What are the biological needs for calcium for an average 70 kg male? Where does most of the calcium go to in the body, and what are some of its important functions?
They need 600-1600 mg calcium per day. Most of the calcium is going to go towards structural support for bones and the rest will be circulating in the blood.
Calcium is also important for muscle contraction, for nerve pulse transmission, for blood clotting, and coenzymes.
What are the biological needs for phosphorus for an average 70 kg male? Where does most of the phosphorus go in the body and what are some of its important functions?
They need 600-2000 mg of phosphorus each day. The bones have about 90% of the body’s phosphorus. It’s important for metabolism, DNA/RNA, phospholipids, specific enzyme components and membrane structure.
Where does calcium and phosphorus mostly come from in our diet?
Dairy products. Calcium also comes in leafy greens as well.
What happens to our bones if you do not get enough calcium and phosphorus from your diet? Why?
Calcium and phosphorus will be taken from your bones in order to supplement the deficiency. You will develop brittle/weaker bones (osteoporosis.) If there’s not enough calcium, the calcium will be taken from our bones.
Why are calcium levels in the blood extremely regulated?
The reason that plasma concentrations of calcium are maintained at a very narrow limit is because you can have a lot of issues (nerve impulses).
What are the three primary tissues that calcium and phosphorus are involved in?
Intestines: absorption of calcium from diet
Bones
Kidneys: filter/reabsorb calcium from plasma
What diseases are caused by improper calcium control and uptake? Are men and women more likely to be affected by these diseases? What age does this usually occur? Are any other individuals likely to develop diseases associated with a deficiency of calcium?
When it comes to improper calcium levels, it can cause osteoporosis. Not having enough calcium prevents your bones from being as hard as they could be.
Women are more likely to get these diseases. Menopause is when females are no longer releasing eggs and it changes everything. Men are prone to osteoporosis after 90 y/o.
People who are anorexic are also prone to developing brittle bones. People who also have family members with osteoporosis are more likely to develop it.
What buffer is present in our blood? What buffer is present in our cells?
Carbonic acid buffer is present in our blood.
Phosphate buffer is present in our cells.
Outside of our bones, where does the rest of the body’s calcium exist? Why are calcium levels in our cytosol low? Which form of calcium is regulated?
Calcium exists in our extracellular fluid and intracellular fluid. About 50% of our body’s calcium is free Ca++ and the other 50% is bound to proteins in soft tissue. Only ionizable calcium is regulated, anything that is bound or part of another molecule is not regulated as the ionized form of calcium. Calcium in the cytosol is low because it’s hiding in the endoplasmic or sarcoplasmic reticulum
What regulatory and structural roles does calcium serve in the body?
Regulatory: calcium plays a role in enzymes and it also has hormone like activity (certain amount of calcium will activate certain signals. Calcium can also go between cells to signal across a synapse or to signal a muscle cell to contract.
Structural: bones and teeth
The concentration of extracellular calcium levels is tightly controlled. What would happen if you were to go below these limits? What would cause you to go outside these limits? What effects would this cause?
What can happen: hypocalcemia
Causes: hypoparathyroidism, vitamin D deficiency, chronic kidney disease
Results: Osteoporosis, neuromuscular irritability. This happens because the excitability of the cell membranes increase when extracellular calcium concentrations are low. As a result, because of this low calcium which causes this increased excitability of the neurons, the action potential threshold becomes lowered to almost the resting potential. This can cause muscle failure (not being able to pump blood properly and not being able to propagate signals properly, which can be deadly).
The concentration of extracellular calcium levels is tightly controlled (within narrow limits).
What would happen if you were to go above of these narrow limits, what would cause you to go outside these limits, and what effects would this cause?
Going above (hypercalcemia) is rare. It’s usually acute or chronic.
Acute: can lead to nausea and vomiting. It can lead to polyuria, coma, depression, confusion, low heart rate, first degree atrio-ventricular block, issues with the heart contracting properly.
Chronic: can lead to pancreatitis, constipation, actual kidney diseases, development of overall neuro-muscular weakness, hypertension, sensitivity of your neurons overfiring
Exchange of calcium occurs between what two domains in the body?
Exchange of calcium occurs between the bones and the extracellular fluid. Release of calcium from the bones or sequestration of calcium by the bones depends on levels of calcium in the extracellular fluid.
Explain what happens to the calcium and phosphorus you obtain from food after you eat and where they go in your body.
Calcium and phosphate will enter the small intestine and then get absorbed pretty readily. Some excretion of calcium and phosphorus will occur through the intestines. Phosphorus is usually absorbed with calcium in the small intestines.
Calcium and phosphorus that was absorbed by intestines will diffuse into extracellular fluid. Phosphorus and calcium are usually deposited at the same time in bone from the extracellular.
Kidneys play a role in reabsorption of phosphorus and calcium that is filtered out from the blood. Excretion of calcium and phosphorus will also occur if there is too much, such that levels of phosphorus and calcium in the extracellular fluid are maintained to proper levels. We also excrete calcium through sweat.
What are the two main types of bone and what proportion of our bones do they make up?
Cortical bone: hard/dense bone that weighs the most (80% of the bone)
Trabecular bone: spongy bone. This makes up 20% of the bone density
Where is the actual calcified portion of your bone?
Bone begins as osteoid (uncalcified, unmineralized portion of bone) and calcium deposits are stored here as calcium hydroxyapatite crystals. When the osteoid becomes calcified/mineralized, it becomes bone.
List and describe each of the bone cells that we covered in class (five in total).
Osteoblasts: bone building cells - forms bones structure
Osteoclasts: bone destroying cells - breaks down bone structures. Important because your bone has to be recycled.
Osteocytes: the actual bone cells.
Osteoprogenitor cells (aka osteogenic cells): specific stem cells that produce osteoblasts (to lead to production of osteocytes).
Chondrocytes: cartilage cells. When you are born, you start out with cartilage which later hardens to bone (chondrocytes part of bone making process). Cartilage in adults are usually in joints, helps lubricate things.
How are osteoclasts formed? Where do these osteoclasts reside, and what role do they serve?
Formed from hematopoietic cells. Several enzymes come in and stimulate the osteoclasts maturation.
Mature osteoclasts sit on the surface of the bony matrix and eat at the bone which will release calcium. The osteoclasts does this through the release of hydrolytic enzymes which help break down the bone.
What is the LRP5 gene responsible for
Why might drug targets for this be helpful for people with osteoporosis?
The LRP5 (low-density lipoprotein receptor-related protein 5) gene is a gene which is involved in bone density.
Mutations in this LRP5 gene allows people to over deposit calcium and calcified bone - therefore individuals with mutations in this gene end up having really, really dense bones.
LRP5 (pathway proteins) could be a potential drug target for people who have things like osteoporosis.
Where is most of our body’s phosphorus stored?
Are phosphorus concentrations tightly controlled?
Most of our body’s phosphorus is stored in the bones (90%), however phosphorus does exist in the blood as well (3.5 mg/L of phosphorus in the blood - a lot of the phosphorus in the blood exists as free ions, some of it is complexed with other types of cations, and some of it is bound to proteins).
Not tightly controlled, but it works similarly to calcium. It gets absorbed and excreted through intestins.
