Question

A. Discuss what homeostatic mechanisms ensure optimal athletic performance when preforming CrossFit activates. Think about electrolytic, acid-base, and fluid balance. Include hormones and their mechanisms of action.

B. Discuss the physiological consequences of renal failure in these three processes.

C. How do metabolic imbalances impact athletic performance during CrossFit?

Answer 1

A)

Fluid and Electrolyte Balance

The kidneys are essential for regulating the volume and composition of bodily fluids. This page outlines key regulatory systems involving the kidneys for controlling volume, sodium and potassium concentrations, and the pH of bodily fluids.

A most critical concept for you to understand is how water and sodium regulation are integrated to defend the body against all possible disturbances in the volume and osmolarity of bodily fluids. Simple examples of such disturbances include dehydration, blood loss, salt ingestion, and plain water ingestion.

Water balance

Water balance is achieved in the body by ensuring that the amount of water consumed in food and drink (and generated by metabolism) equals the amount of water excreted. The consumption side is regulated by behavioral mechanisms, including thirst and salt cravings. While almost a liter of water per day is lost through the skin, lungs, and feces, the kidneys are the major site of regulated excretion of water.

One way the the kidneys can directly control the volume of bodily fluids is by the amount of water excreted in the urine. Either the kidneys can conserve water by producing urine that is concentrated relative to plasma, or they can rid the body of excess water by producing urine that is dilute relative to plasma.

Direct control of water excretion in the kidneys is exercised by vasopressin, or anti-diuretic hormone (ADH), a peptide hormone secreted by the hypothalamus. ADH causes the insertion of water channels into the membranes of cells lining the collecting ducts, allowing water reabsorption to occur. Without ADH, little water is reabsorbed in the collecting ducts and dilute urine is excreted.

ADH secretion is influenced by several factors (note that anything that stimulates ADH secretion also stimulates thirst):

1. By special receptors in the hypothalamus that are sensitive to increasing plasma osmolarity (when the plasma gets too concentrated). These stimulate ADH secretion.

2. By stretch receptors in the atria of the heart, which are activated by a larger than normal volume of blood returning to the heart from the veins. These inhibit ADH secretion, because the body wants to rid itself of the excess fluid volume.

3. By stretch receptors in the aorta and carotid arteries, which are stimulated when blood pressure falls. These stimulate ADH secretion, because the body wants to maintain enough volume to generate the blood pressure necessary to deliver blood to the tissues.

Sodium balance

In addition to regulating total volume, the osmolarity (the amount of solute per unit volume) of bodily fluids is also tightly regulated. Extreme variation in osmolarity causes cells to shrink or swell, damaging or destroying cellular structure and disrupting normal cellular function.

Regulation of osmolarity is achieved by balancing the intake and excretion of sodium with that of water. (Sodium is by far the major solute in extracellular fluids, so it effectively determines the osmolarity of extracellular fluids.)

An important concept is that regulation of osmolarity must be integrated with regulation of volume, because changes in water volume alone have diluting or concentrating effects on the bodily fluids. For example, when you become dehydrated you lose proportionately more water than solute (sodium), so the osmolarity of your bodily fluids increases. In this situation the body must conserve water but not sodium, thus stemming the rise in osmolarity. If you lose a large amount of blood from trauma or surgery, however, your loses of sodium and water are proportionate to the composition of bodily fluids. In this situation the body should conserve both water and sodium.

As noted above, ADH plays a role in lowering osmolarity (reducing sodium concentration) by increasing water reabsorption in the kidneys, thus helping to dilute bodily fluids. To prevent osmolarity from decreasing below normal, the kidneys also have a regulated mechanism for reabsorbing sodium in the distal nephron. This mechanism is controlled by aldosterone, a steroid hormone produced by the adrenal cortex. Aldosterone secretion is controlled two ways:

1.The adrenal cortex directly senses plasma osmolarity. When the osmolarity increases above normal, aldosterone secretion is inhibited. The lack of aldosterone causes less sodium to be reabsorbed in the distal tubule. Remember that in this setting ADH secretion will increase to conserve water, thus complementing the effect of low aldosterone levels to decrease the osmolarity of bodily fluids. The net effect on urine excretion is a decrease in the amount of urine excreted, with an increase in the osmolarity of the urine.

2. The kidneys sense low blood pressure (which results in lower filtration rates and lower flow through the tubule). This triggers a complex response to raise blood pressure and conserve volume. Specialized cells (juxtaglomerular cells) in the afferent and efferent arterioles produce renin, a peptide hormone that initiates a hormonal cascade that ultimately produces angiotensin II. Angiotensin II stimulates the adrenal cortex to produce aldosterone.

In this setting, where the body is attempting to conserve volume, ADH secretion is also stimulated and water reabsorption increases. Because aldosterone is also acting to increase sodium reabsorption, the net effect is retention of fluid that is roughly the same osmolarity as bodily fluids. The net effect on urine excretion is a decrease in the amount of urine excreted, with lower osmolarity than in the previous example.

ACID-BASE BALANCE

Proper physiological functioning depends on a very tight balance between the concentrations of acids and bases in the blood. Acid-balance balance is measured using the pH scale, as shown in Figure 1. A variety of buffering systems permits blood and other bodily fluids to maintain a narrow pH range, even in the face of perturbations. A buffer is a chemical system that prevents a radical change in fluid pH by dampening the change in hydrogen ion concentrations in the case of excess acid or base. Most commonly, the substance that absorbs the ions is either a weak acid, which takes up hydroxyl ions, or a weak base, which takes up hydrogen ions.

BUFFER SYSTEMS IN THE BODY

The buffer systems in the human body are extremely efficient, and different systems work at different rates. It takes only seconds for the chemical buffers in the blood to make adjustments to pH. The respiratory tract can adjust the blood pH upward in minutes by exhaling CO₂ from the body. The renal system can also adjust blood pH through the excretion of hydrogen ions (H⁺) and the conservation of bicarbonate, but this process takes hours to days to have an effect.

The buffer systems functioning in blood plasma include plasma proteins, phosphate, and bicarbonate and carbonic acid buffers. The kidneys help control acid-base balance by excreting hydrogen ions and generating bicarbonate that helps maintain blood plasma pH within a normal range. Protein buffer systems work predominantly inside cells.

PROTEIN BUFFERS IN BLOOD PLASMA AND CELLS

Nearly all proteins can function as buffers. Proteins are made up of amino acids, which contain positively charged amino groups and negatively charged carboxyl groups. The charged regions of these molecules can bind hydrogen and hydroxyl ions, and thus function as buffers. Buffering by proteins accounts for two-thirds of the buffering power of the blood and most of the buffering within cells.

HEMOGLOBIN AS A BUFFER

Hemoglobin is the principal protein inside of red blood cells and accounts for one-third of the mass of the cell. During the conversion of CO₂ into bicarbonate, hydrogen ions liberated in the reaction are buffered by hemoglobin, which is reduced by the dissociation of oxygen. This buffering helps maintain normal pH. The process is reversed in the pulmonary capillaries to re-form CO₂, which then can diffuse into the air sacs to be exhaled into the atmosphere. This process is discussed in detail in the chapter on the respiratory system.

PHOSPHATE BUFFER

Phosphates are found in the blood in two forms: sodium dihydrogen phosphate (Na₂H₂PO₄⁻), which is a weak acid, and sodium monohydrogen phosphate (Na₂HPO42-), which is a weak base. When Na₂HPO42- comes into contact with a strong acid, such as HCl, the base picks up a second hydrogen ion to form the weak acid Na₂H₂PO₄⁻ and sodium chloride, NaCl. When Na₂HPO42− (the weak acid) comes into contact with a strong base, such as sodium hydroxide (NaOH), the weak acid reverts back to the weak base and produces water. Acids and bases are still present, but they hold onto the ions.

HCl + Na₂HPO₄→NaH₂PO₄ + NaCl

(strong acid) + (weak base) → (weak acid) + (salt)

NaOH + NaH₂PO₄→Na₂HPO₄ + H₂O

(strong base) + (weak acid) → (weak base) + (water)

BICARBONATE-CARBONIC ACID BUFFER

The bicarbonate-carbonic acid buffer works in a fashion similar to phosphate buffers. The bicarbonate is regulated in the blood by sodium, as are the phosphate ions. When sodium bicarbonate (NaHCO₃), comes into contact with a strong acid, such as HCl, carbonic acid (H₂CO₃), which is a weak acid, and NaCl are formed. When carbonic acid comes into contact with a strong base, such as NaOH, bicarbonate and water are formed.

NaHCO₃ + HCl →  H₂CO₃+NaCl

(sodium bicarbonate) + (strong acid) → (weak acid) + (salt)

H₂CO₃ + NaOH→HCO_3- + H₂O

(weak acid) + (strong base)→(bicarbonate) + (water)

As with the phosphate buffer, a weak acid or weak base captures the free ions, and a significant change in pH is prevented. Bicarbonate ions and carbonic acid are present in the blood in a 20:1 ratio if the blood pH is within the normal range. With 20 times more bicarbonate than carbonic acid, this capture system is most efficient at buffering changes that would make the blood more acidic. This is useful because most of the body’s metabolic wastes, such as lactic acid and ketones, are acids. Carbonic acid levels in the blood are controlled by the expiration of CO₂ through the lungs. In red blood cells, carbonic anhydrase forces the dissociation of the acid, rendering the blood less acidic. Because of this acid dissociation, CO₂ is exhaled (see equations above). The level of bicarbonate in the blood is controlled through the renal system, where bicarbonate ions in the renal filtrate are conserved and passed back into the blood. However, the bicarbonate buffer is the primary buffering system of the IF surrounding the cells in tissues throughout the body.

RESPIRATORY REGULATION OF ACID-BASE BALANCE

The respiratory system contributes to the balance of acids and bases in the body by regulating the blood levels of carbonic acid (Figure 2). CO₂ in the blood readily reacts with water to form carbonic acid, and the levels of CO₂ and carbonic acid in the blood are in equilibrium. When the CO₂ level in the blood rises (as it does when you hold your breath), the excess CO₂ reacts with water to form additional carbonic acid, lowering blood pH. Increasing the rate and/or depth of respiration (which you might feel the “urge” to do after holding your breath) allows you to exhale more CO₂. The loss of CO₂ from the body reduces blood levels of carbonic acid and thereby adjusts the pH upward, toward normal levels. As you might have surmised, this process also works in the opposite direction. Excessive deep and rapid breathing (as in hyperventilation) rids the blood of CO₂ and reduces the level of carbonic acid, making the blood too alkaline. This brief alkalosis can be remedied by rebreathing air that has been exhaled into a paper bag. Rebreathing exhaled air will rapidly bring blood pH down toward normal.

The chemical reactions that regulate the levels of CO₂ and carbonic acid occur in the lungs when blood travels through the lung’s pulmonary capillaries. Minor adjustments in breathing are usually sufficient to adjust the pH of the blood by changing how much CO₂ is exhaled. In fact, doubling the respiratory rate for less than 1 minute, removing “extra” CO₂, would increase the blood pH by 0.2. This situation is common if you are exercising strenuously over a period of time. To keep up the necessary energy production, you would produce excess CO₂ (and lactic acid if exercising beyond your aerobic threshold). In order to balance the increased acid production, the respiration rate goes up to remove the CO₂. This helps to keep you from developing acidosis.

The body regulates the respiratory rate by the use of chemoreceptors, which primarily use CO₂ as a signal. Peripheral blood sensors are found in the walls of the aorta and carotid arteries. These sensors signal the brain to provide immediate adjustments to the respiratory rate if CO₂ levels rise or fall. Yet other sensors are found in the brain itself. Changes in the pH of CSF affect the respiratory center in the medulla oblongata, which can directly modulate breathing rate to bring the pH back into the normal range.

Hypercapnia, or abnormally elevated blood levels of CO₂, occurs in any situation that impairs respiratory functions, including pneumonia and congestive heart failure. Reduced breathing (hypoventilation) due to drugs such as morphine, barbiturates, or ethanol (or even just holding one’s breath) can also result in hypercapnia. Hypocapnia, or abnormally low blood levels of CO₂, occurs with any cause of hyperventilation that drives off the CO₂, such as salicylate toxicity, elevated room temperatures, fever, or hysteria.

RENAL REGULATION OF ACID-BASE BALANCE

The renal regulation of the body’s acid-base balance addresses the metabolic component of the buffering system. Whereas the respiratory system (together with breathing centers in the brain) controls the blood levels of carbonic acid by controlling the exhalation of CO₂, the renal system controls the blood levels of bicarbonate. A decrease of blood bicarbonate can result from the inhibition of carbonic anhydrase by certain diuretics or from excessive bicarbonate loss due to diarrhea. Blood bicarbonate levels are also typically lower in people who have Addison’s disease (chronic adrenal insufficiency), in which aldosterone levels are reduced, and in people who have renal damage, such as chronic nephritis. Finally, low bicarbonate blood levels can result from elevated levels of ketones (common in unmanaged diabetes mellitus), which bind bicarbonate in the filtrate and prevent its conservation.

Bicarbonate ions, HCO₃^–, found in the filtrate, are essential to the bicarbonate buffer system, yet the cells of the tubule are not permeable to bicarbonate ions. The steps involved in supplying bicarbonate ions to the system are

• Step 1: Sodium ions are reabsorbed from the filtrate in exchange for H⁺ by an antiport mechanism in the apical membranes of cells lining the renal tubule.
• Step 2: The cells produce bicarbonate ions that can be shunted to peritubular capillaries.
• Step 3: When CO₂ is available, the reaction is driven to the formation of carbonic acid, which dissociates to form a bicarbonate ion and a hydrogen ion.
• Step 4: The bicarbonate ion passes into the peritubular capillaries and returns to the blood. The hydrogen ion is secreted into the filtrate, where it can become part of new water molecules and be reabsorbed as such, or removed in the urine.

It is also possible that salts in the filtrate, such as sulfates, phosphates, or ammonia, will capture hydrogen ions. If this occurs, the hydrogen ions will not be available to combine with bicarbonate ions and produce CO₂. In such cases, bicarbonate ions are not conserved from the filtrate to the blood, which will also contribute to a pH imbalance and acidosis.

The hydrogen ions also compete with potassium to exchange with sodium in the renal tubules. If more potassium is present than normal, potassium, rather than the hydrogen ions, will be exchanged, and increased potassium enters the filtrate. When this occurs, fewer hydrogen ions in the filtrate participate in the conversion of bicarbonate into CO₂ and less bicarbonate is conserved. If there is less potassium, more hydrogen ions enter the filtrate to be exchanged with sodium and more bicarbonate is conserved.

Chloride ions are important in neutralizing positive ion charges in the body. If chloride is lost, the body uses bicarbonate ions in place of the lost chloride ions. Thus, lost chloride results in an increased reabsorption of bicarbonate by the renal system.

B)

As the site of production of the hormones: renin, erythropoietin and calcitriol that regulate, respectively, blood pressure, erythrocyte (red blood cell) production and absorption of dietary calcium, the kidneys have significant and disparate endocrine function. Additionally, of course, the kidneys have an excretory function in the formation of urine from filtered blood. Urine is not just a vehicle for excretion of a range of substances; its formation has vital homeostatic significance.

By their ability to continuously adjust both the volume and chemical composition of urine, the kidneys help to ensure that the volume, pH and chemical composition of fluid (both intracellular and extracellular) within the body remains constant. The constancy of this internal environment is essential for cell function and ultimately life itself. This general homeostatic role of the kidney includes preserving two particular aspects of blood chemistry, pH and electrolyte content.

Both the maintenance of blood pH within narrow limits, 7.35-7.45 (i.e. normal acid-base balance), and the maintenance of plasma sodium and potassium concentrations within narrow limits, (135-145 mmol/L and 3.5-5.2 mmol/L respectively), are dependent on normally functioning kidneys.

Given these physiological (homeostatic) aspects of kidney function, it is no surprise that chronic kidney disease (CKD) can be associated with disturbance of both acid-base balance and plasma electrolyte concentration. These complications, which are potential causes of significant morbidity and mortality for patients with CKD, are the sole focus of the September 2017 issue of the journal Advances in Chronic Kidney Disease.

This themed issue comprises nine articles written by experts in the field. Four of these address various aspects of acid-base disturbance in CKD, three address aspects of disturbed potassium homeostasis in CKD, and two address aspects of disturbed sodium homeostasis in CKD.

C)

• Extreme muscle weakness

Poor muscular endurance – essentially gassing out early in an exercise and not having much strength – can be caused by an electrolyte imbalance, says Doctor Zyrowski.

• Muscle cramping and twitching

Another symptom includes starting to get a lot of different spasms and muscle cramps. “A lot of times they start in the small muscle groups: the hands, the feet, around the mouth, around the eyes. Then they can go on into the big muscle groups,” explains Doctor Zyrowski.

• Lethargy and headaches

Sodium controls whether water moves in or out of cells. When an imbalance occurs and brain cells are affected, headaches, confusion and lethargy are common symptoms.

• Fatigue

Fatigue is often associated with electrolyte imbalances and can be a big hinderance for athletes.

• Frequent thirst

“This is where you feel like you just want to drink more and more water, yet you’ve been drinking enough water, but you still feel thirsty,” describes Doctor Zyrowski. When you can’t quench that thirst, that’s typically an electrolyte imbalance.

• Frequent urination

Frequent urination is usually a result of frequent thirst and excessive water ingestion, but can also be caused by lack of electrolytes.

Optimise your hydration and electrolyte levels

Long periods of exercise, particularly in the heat, can cause significant electrolyte loss. These electrolytes can usually be replaced by food and drink; however, certain populations may want to consider supplementing with electrolyte-rich drinks to replace their losses.