Lecture 2 1/24/25 Flashcards
What are the consequences of mitochondrial dysfunction?
-defective electron transport chain
-mitochondrial pore opening
-cell death
Which channels allow for calcium to enter the cell?
-ligand-gated channels controlled by hormones and neurotransmitters
-voltage-gated channels controlled by electric membrane potential
Which channels allow for calcium to exit the cell?
-ATP-dependent calcium pump
-sodium/calcium exchanger
Where is calcium stored within the cell?
storage organelles such as the mitochondria and smooth ER
Which functions are free/ionized calcium involved in?
-neuron action potentials
-muscle contraction
-hormone secretion
-blood coagulation
-intracellular functions
What are the characteristics of free/ionized calcium?
-most biologically active
-regulated by the body
-imbalance leads to pathology
What are the characteristics of complexed calcium?
-bound to non-protein anions
-electrically neutral
-small enough to diffuse across cell membranes
-not useful for cellular processes
What are the characteristics of protein-bound calcium?
-bound to negatively charged proteins
-80% bound to albumin, 20% bound to globulins
-too large to cross membranes
-not involved in cellular processes
-acts as buffer storage pool
What is the percentage of each calcium “fraction” in the plasma?
-free/ionized: 50-55%
-protein-bound: 40-45%
-complexed: 5-10%
What are the characteristics of total calcium measurement in blood?
-measures all fractions
-want a fasted, non-lipemic, non-hemolyzed sample
-poor correlation between total calcium and ionized calcium; must measure ionized calcium separately
What is the total body calcium distribution?
-99% in the bone
-1% in the plasma, separated into fractions
What is the role of the skeleton in terms of calcium?
stores calcium and phosphorus in the form of hydroxyapatite
What is bone resorption?
process in which osteoclasts break down and release minerals into the blood stream
How does PTH impact bone resorption?
increases osteoclast activity and bone resorption
What are the characteristics of PTH-independent calcium reabsorption in the kidneys?
-99% of filtered calcium is absorbed
-mostly occurs in proximal tubule
What are the characteristics of PTH-dependent calcium reabsorption in the kidneys?
-occurs in ascending loop and distal tubule
-PTH increases renal calcium absorption
what is renal reabsorption?
process by which the nephrons remove water and solutes from the tubular fluid and return them to circulating blood
What are the characteristics of renal reabsorption of phosphorus?
-filtered at glomerulus
-around 90% reabsorbed
-primarily reabsorbed in proximal tubule
-PTH decreases amount of phosphorus that is reabsorbed
What are the characteristics of parathyroid hormone?
-regulates minute-to-minute ionized calcium
-secreted by chief cells in the parathyroid gland
-short half life and limited storage prevents over-correction
What is the production feedback loop involving calcium and PTH?
-decreased calcium stimulates the parathyroid glands
-parathyroid glands release PTH
-PTH regulates calcium setpoint to increase calcium
How does PTH act on the bone?
increases bone resorption to increase calcium
How does PTH act on the kidney?
-increases tubular calcium reabsorption to increase calcium
-increases calcitriol activation to increase intestinal absorption of calcium
What is the inhibition feedback loop involving calcium and PTH?
increased calcium inhibits PTH production, decreasing bone resorption, renal reabsorption, and calcitriol production
What is the feedback loop involving phosphorus and PTH?
-PTH promotes excretion of phosphorus by the kidneys to lower phosphorus levels
-low phosphorus prevents further production of PTH
What are the potential triggers for PTH release?
-low calcium
-high phosphorus
-low calcitriol
What is the net effect of PTH on plasma conc.?
-increased calcium
-decreased phosphorus
-increased calcitriol
What are the characteristics of calcitriol?
-active form of vitamin D3
-fat soluble vitamin obtained from diet
-activated in the kidney
What are the effects of calcitriol?
-increases calcium and phosphorus absorption in the intestines
-increases resorption of calcium and phosphorus from bone
-increases renal reabsorption of calcium and phosphorus
What is the feedback loop involving calcitriol and PTH?
-increased calcitriol decreases PTH production/release
-decreased calcitriol increases PTH production/release
What are the characteristics of calcitonin?
-opposes PTH’s effect on calcium and “tones down” calcium
-produced by the parafollicular cells/C cells of the thyroid gland
-decreases postprandial hypercalcemia
-decreases bone resorption
What are the characteristics of PTH-related protein?
-cause of humoral hypercalcemia of malignancy
-produced by some tumors, including anal sac adenocarcinoma, lymphoma, and multiple myeloma
-same biological function as PTH; increases Ca, decreases P
What are the characteristics of PTH-rP measurement?
-normally not detected
-if present, diagnostic for neoplasia
-not produced by all tumors, so absence of PTH-rP does not rule out neoplasia
What is the importance of evaluating Ca and P together?
if Ca x P is greater than or equal to 60-80, it indicates an increased risk for metastatic mineralization of tissues
