BME 5010, CHAPTER 16C, D: THE KIDNEYS (RENAL PHYSIOLOGY)

BME 5010, CHAPTER 16C, D: THE KIDNEYS (RENAL PHYSIOLOGY)


KEY WORDS	MEANING
CALCIUM REGULATION	Maintaining calcium homeostasis is important. Low extracellular calcium concentration increases the excitability of nerve and muscle cell membranes, and can produce spasm. High calcium concentration causes cardiac arrhythmias and depressed neuromuscular excitability.
SITES FOR CALCIUM HOMEOSTASIS Fig 16-27 Table 16-6 (Do not need to know).	Bone contains 99% of the body's calcium. Bone has a collagen matrix called osteoid upon which is built crystals of calcium and phosphate (hydroxyapatite crystals). There are 3 types of bone cells: 1) Osteoblasts - bone-forming cells. 2) Osteocytes - former osteoblasts 3) Osteoclasts - break down bone The interplay of these cells and the hormones that influence bone mass constantly remodel bone. Bone acts as a reservoir of calcium that goes into the plasma and a sink for calcium coming from the plasma. Bone remodeling is influenced by mechanical stresses and hormones.
Kidneys	About 60% of calcium is filtered in the glomerulus and reabsorbed in the renal tubules. (The rest is bound to plasma protein). As for sodium, the control of calcium excretion is exerted mainly on reabsorption. When plasma calcium is high, less is reabsorbed and vice versa, by reflex responses.
Parathyroid hormone (PH)	Produced by the parathyroid glands which are embedded in the surface of the thyroid glands. Parathyroid cells have calcium receptors. Decreased plasma calcium stimulates secretion of parathyroid hormone. Parathyroid hormone (PH) acts to increase blood calcium levels as follows: 1) It moves calcium from bone to plasma. 2) It activates an enzyme in the kidney that activates vitamin D. 3) Increases renal tubular reabsorption of calcium
Vitamin D Or1,25-(OH)₂D₃ Figs 16-28, 16-29	Vitamin D denotes a group of closely related compounds. It promotes calcium absorption from the intestine into the body. Formation of vitamin D: (1) UV radiation converts a cholesterol derivative in the skin to vitamin D. (2) It is ingested in food, esp plants. (3) These forms have hydroxyl (-OH) added in the liver and kidney. The enzyme that catalyzes this reaction in the kidneys is activated by parathyroid hormone. (4) This activated form then promotes calcium absorption from the intestines.
Metabolic bone diseases	Rickets and osteomalacia: Lack of bone mineralization. In rickets there is a lack of vitamin D so not enough calcium is absorbed from the intestines to make mineralized bone. Osteoporosis: Both the cartilage matrix and the minerals are lost. It is seen more in elderly women than men: women have a smaller bone mass to begin with and menopause removes the bone-building aspects of estrogen. Osteoporosis in post-menopausal women causes 1.5 million fractures each year and thousands of deaths. Prevention is through adequate dietary calcium (1000 mg/day and 1200-1500 mg/day after menopause), a weight-bearing exercise program, and estrogen therapy to reduce the rate of bone loss.

HYDROGEN-ION REGULATION

Metabolic reactions in the body are highly sensitive to pH or hydrogen ion concentration. Hydrogen ions change shapes of proteins, including enzymes, so H⁺ changes can greatly effect the chemical reactions in your body. Normal pH of blood is about 7.4. There are several homeostatic mechanisms to maintain blood pH to 7.4, as follows:

Homeostasis

H⁺ ions are created and destroyed all the time. In the face of this the body needs to maintain a narrow range of free H⁺ concentration to function. How is H⁺ so narrowly controlled? Through (1) buffers, (2) the lungs and (3) the kidneys.

Sources of hydrogen ion gain.

(1) CO₂ + H₂0 ==== H₂CO₃ ====

HCO₃^- + H⁺

(2) Protein breakdown.
(3) Loss of bicarbonate in GI tract.
(4) Loss of bicarbonate in kidney.

(3) and (4) result in a gain of plasma H⁺ because HCO₃^- is no longer available to bind H⁺.

Sources of hydrogen ion loss.

(1) Loss of H⁺ from stomach in vomiting.

(2) Loss of H⁺ in urine.

(3) Hypoventilation.

Buffering of H⁺ in the body.

Any substance that can reversibly bind H⁺ is called a buffer. HCO₃^- (bicarbonate ion) is an important buffer.

Buffer^- + H⁺ === Hbuffer

When H⁺ increases, the reaction is forced to the right and more H⁺ is bound to buffer.

Homeostasis of H⁺ by the lungs

Besides buffers, H⁺ levels are controlled by the lungs.

When H⁺ is high the lungs reflexively increase their ventilation and this blows off CO₂, decreasing PCO₂ and decreasing H⁺.

Homeostasis of H⁺ by the kidneys

Excreting a bicarbonate (HCO₃^-) in the urine results in a free H⁺ in the plasma, because an HCO₃^- that would bind H⁺ has been eliminated.

When H⁺ is lowered in the body (alkalosis) the kidney excretes HCO₃^- to free up H⁺ in the plasma.

When H⁺ is raised in the body (acidosis), the kidney tubules produce bicarbonate and add it to the urine.

Bicarbonate filtration and reabsorption.

Figs 16-30

Bicarbonate is freely filtered in the renal corpuscles. It undergoes marked tubular reabsorption in the proximal tubules and collecting ducts.

Bicarbonate is reabsorbed as follows: In the tubular epithelial cells:

CO₂ + H₂0 ==== H₂CO₃ (via carbonic anhydrase) ==== HCO₃^- + H⁺

The HCO₃^- diffuses down its concentration gradient into the plasma. The H⁺ is secreted into the tubule. This combines with filtered HCO₃^- to form CO₂ and H₂0. The net effect is reabsorption of one HCO₃^- for each one filtered, even though it is not the same one.
If plasma HCO₃^- is low, the H⁺ combines with other buffers. HCO₃^- is still produced in the renal tubules and diffuses into the plasma, raising plasma HCO₃^-.

Kidney responses to acidosis.

(1) H⁺ is secreted to reabsorb all the filtered bicarbonate as in Fig 16-30.

(2) More H⁺ is secreted to bind to other buffers in the urine as in Fig 16-31. More HCO₃^- is created and diffuses into the plasma, to bind H⁺ and make the plasma more alkaline.

(3) Glutamine metabolism and ammonium (NH₄+) excretion increase. Ammonium grabs H⁺ and HCO₃^- goes into the plasma, making it more alkaline. Fig 16-32.

The signals to do the above in response to increased plasma H⁺ are complex and will not be covered here.

Kidney responses to alkalosis

(1) H⁺ secretion is down, so H⁺ cannot reabsorb all the bicarbonate. A significant amount of bicarbonate is excreted in the urine.

(2) Glutamine metabolism and ammonium excretion are down, so little bicarbonate goes into the plasma.

Acidosis and alkalosis

Table 16-9

Respiratory acidosis results from the failure of the lungs to eliminate CO₂ fast enough. CO₂ builds up in the plasma. This increase H+ as follows:

CO₂ + H₂0 ==== H₂CO₃ (via carbonic anhydrase) ==== HCO₃^- + H⁺

Metabolic acidosis can result from lactic acid in strenuous exercise, ketone bodies in diabetes and getting rid of too much bicarbonate in diarrhea.

Respiratory alkalosis can result from hyperventilating and blowing off too much CO₂.

Metabolic alkalosis can result from persistent vomiting which eliminates H⁺ from the stomach.

In the metabolic cases the lungs will reflexively hypo- or hyperventilate to compensate.

The kidneys will compensate in the metabolic or respiratory cases. In acidosis, the kidneys will secrete H⁺ and reabsorb HCO₃^-. In alkalosis, the kidney rids of body of HCO₃^-.

HYDROGEN-ION REGULATION	Metabolic reactions in the body are highly sensitive to pH or hydrogen ion concentration. Hydrogen ions change shapes of proteins, including enzymes, so H⁺ changes can greatly effect the chemical reactions in your body. Normal pH of blood is about 7.4. There are several homeostatic mechanisms to maintain blood pH to 7.4, as follows:
Homeostasis	H⁺ ions are created and destroyed all the time. In the face of this the body needs to maintain a narrow range of free H⁺ concentration to function. How is H⁺ so narrowly controlled? Through (1) buffers, (2) the lungs and (3) the kidneys.
Sources of hydrogen ion gain.	(1) CO₂ + H₂0 ==== H₂CO₃ ==== HCO₃^- + H⁺ (2) Protein breakdown. (3) Loss of bicarbonate in GI tract. (4) Loss of bicarbonate in kidney. (3) and (4) result in a gain of plasma H⁺ because HCO₃^- is no longer available to bind H⁺.
Sources of hydrogen ion loss.	(1) Loss of H⁺ from stomach in vomiting. (2) Loss of H⁺ in urine. (3) Hypoventilation.
Buffering of H⁺ in the body.	Any substance that can reversibly bind H⁺ is called a buffer. HCO₃^- (bicarbonate ion) is an important buffer. Buffer^- + H⁺ === Hbuffer When H⁺ increases, the reaction is forced to the right and more H⁺ is bound to buffer.
Homeostasis of H⁺ by the lungs	Besides buffers, H⁺ levels are controlled by the lungs. When H⁺ is high the lungs reflexively increase their ventilation and this blows off CO₂, decreasing PCO₂ and decreasing H⁺.
Homeostasis of H⁺ by the kidneys	Excreting a bicarbonate (HCO₃^-) in the urine results in a free H⁺ in the plasma, because an HCO₃^- that would bind H⁺ has been eliminated. When H⁺ is lowered in the body (alkalosis) the kidney excretes HCO₃^- to free up H⁺ in the plasma. When H⁺ is raised in the body (acidosis), the kidney tubules produce bicarbonate and add it to the urine.
Bicarbonate filtration and reabsorption. Figs 16-30	Bicarbonate is freely filtered in the renal corpuscles. It undergoes marked tubular reabsorption in the proximal tubules and collecting ducts. Bicarbonate is reabsorbed as follows: In the tubular epithelial cells: CO₂ + H₂0 ==== H₂CO₃ (via carbonic anhydrase) ==== HCO₃^- + H⁺ The HCO₃^- diffuses down its concentration gradient into the plasma. The H⁺ is secreted into the tubule. This combines with filtered HCO₃^- to form CO₂ and H₂0. The net effect is reabsorption of one HCO₃^- for each one filtered, even though it is not the same one. If plasma HCO₃^- is low, the H⁺ combines with other buffers. HCO₃^- is still produced in the renal tubules and diffuses into the plasma, raising plasma HCO₃^-.
Kidney responses to acidosis.	(1) H⁺ is secreted to reabsorb all the filtered bicarbonate as in Fig 16-30. (2) More H⁺ is secreted to bind to other buffers in the urine as in Fig 16-31. More HCO₃^- is created and diffuses into the plasma, to bind H⁺ and make the plasma more alkaline. (3) Glutamine metabolism and ammonium (NH₄+) excretion increase. Ammonium grabs H⁺ and HCO₃^- goes into the plasma, making it more alkaline. Fig 16-32. The signals to do the above in response to increased plasma H⁺ are complex and will not be covered here.
Kidney responses to alkalosis	(1) H⁺ secretion is down, so H⁺ cannot reabsorb all the bicarbonate. A significant amount of bicarbonate is excreted in the urine. (2) Glutamine metabolism and ammonium excretion are down, so little bicarbonate goes into the plasma.
Acidosis and alkalosis Table 16-9	Respiratory acidosis results from the failure of the lungs to eliminate CO₂ fast enough. CO₂ builds up in the plasma. This increase H+ as follows: CO₂ + H₂0 ==== H₂CO₃ (via carbonic anhydrase) ==== HCO₃^- + H⁺ Metabolic acidosis can result from lactic acid in strenuous exercise, ketone bodies in diabetes and getting rid of too much bicarbonate in diarrhea. Respiratory alkalosis can result from hyperventilating and blowing off too much CO₂. Metabolic alkalosis can result from persistent vomiting which eliminates H⁺ from the stomach. In the metabolic cases the lungs will reflexively hypo- or hyperventilate to compensate. The kidneys will compensate in the metabolic or respiratory cases. In acidosis, the kidneys will secrete H⁺ and reabsorb HCO₃^-. In alkalosis, the kidney rids of body of HCO₃^-.

DIURETICS AND KIDNEY DISEASE

Diuretics

Diuretics are drugs used to increase the volume of urine. They inhibit the reabsorption of sodium ions.

They are used mainly in congestive heart failure and in hypertension.

In congestive heart failure (CHF) there is reduced cardiac output, therefore a decreased GFR, therefore a decreased pressure to kidney baroreceptors, and therefore increased renin and aldosterone secretion (to increase blood pressure and volume). Decreased GFR and increased aldosterone retains sodium in the body and edema results. Diuretics are used to rid the body of sodium and water in CHF. These can have the unwanted side effect of increased potassium excretion.

In hypertension, diuretics decrease body sodium and water and lower blood pressure.

Kidney disease

There are many types of kidney disease.

Blocking the urethra or ureter (ie. with kidney stones) can put too much pressure in the kidneys or predispose themto infection.

Autoimmune diseases such as lupus can attack the kidneys, destroying nephrons.

When the kidneys break down nephrons no longer filter blood. This is called uremia: the breakdown products that should be in the urine are now circulating in the blood.

Dialysis

These are artificial means to filter the blood when the kidneys cannot do it.

In hemodialysis blood is pumped from a patient's arteries into cellophane tubing that is bathed in a large volume of fluid with ion concentrations similar to blood. The cellophane is permeable to water and small solutes but not permeable to protein and blood cells. As the blood flows through the tubing, excess ions and wastes diffuse out of the blood down their concentration gradients, cleaning the blood of excess ions and waste products.

In peritoneal dialysis, fluid (with ions) is injected into the abdominal wall. The lining of the abdomen, the peritoneum, is used to filter excess substances from the blood as it flows through the peritoneum. The dialysis fluid is then removed.

Kidney transplant

The treatment of choice in permanent kidney failure. One can function with one kidney. In fact, the kidneys will do their work with as little as 10% of the nephrons functioning. The remaining working nephrons adjust to increase their functional capacity.

DIURETICS AND KIDNEY DISEASE
Diuretics	Diuretics are drugs used to increase the volume of urine. They inhibit the reabsorption of sodium ions. They are used mainly in congestive heart failure and in hypertension. In congestive heart failure (CHF) there is reduced cardiac output, therefore a decreased GFR, therefore a decreased pressure to kidney baroreceptors, and therefore increased renin and aldosterone secretion (to increase blood pressure and volume). Decreased GFR and increased aldosterone retains sodium in the body and edema results. Diuretics are used to rid the body of sodium and water in CHF. These can have the unwanted side effect of increased potassium excretion. In hypertension, diuretics decrease body sodium and water and lower blood pressure.
Kidney disease	There are many types of kidney disease. Blocking the urethra or ureter (ie. with kidney stones) can put too much pressure in the kidneys or predispose themto infection. Autoimmune diseases such as lupus can attack the kidneys, destroying nephrons. When the kidneys break down nephrons no longer filter blood. This is called uremia: the breakdown products that should be in the urine are now circulating in the blood.
Dialysis	These are artificial means to filter the blood when the kidneys cannot do it. In hemodialysis blood is pumped from a patient's arteries into cellophane tubing that is bathed in a large volume of fluid with ion concentrations similar to blood. The cellophane is permeable to water and small solutes but not permeable to protein and blood cells. As the blood flows through the tubing, excess ions and wastes diffuse out of the blood down their concentration gradients, cleaning the blood of excess ions and waste products. In peritoneal dialysis, fluid (with ions) is injected into the abdominal wall. The lining of the abdomen, the peritoneum, is used to filter excess substances from the blood as it flows through the peritoneum. The dialysis fluid is then removed.
Kidney transplant	The treatment of choice in permanent kidney failure. One can function with one kidney. In fact, the kidneys will do their work with as little as 10% of the nephrons functioning. The remaining working nephrons adjust to increase their functional capacity.

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