Hormonal Regulation, Renal Physiology, and Reproductive Health: An In-Depth Guide

Posted on Aug 25, 2024 in Biology

Hormonal Regulation of Renal Sodium Reabsorption

Question: Mention two hormones that would increase renal Na⁺ reabsorption. What are their effects and mechanisms of action? Which segments of the renal tubules do they affect?

Answer:

Two hormones that are secreted to increase Na⁺ reabsorption are:

1. Aldosterone

Aldosterone stimulates Na⁺ reabsorption in principal cells of the distal convoluted tubule (DCT) and cortical collecting duct (CCD). It increases Na⁺ reabsorption in exchange for K⁺ secretion.

Mechanism of Action:

Aldosterone acts via new protein synthesis (slow onset: ½ to 2 hours). It increases the number of Na⁺ channels in the luminal membrane and Na⁺-K⁺ ATPase in the basolateral membrane of principal cells.

2. Angiotensin II

1. Angiotensin II stimulates the secretion of aldosterone.
2. In the proximal convoluted tubule (PCT), it increases Na⁺ reabsorption.

Mechanism of Action:

• It directly stimulates Na⁺-K⁺ ATPase at the basolateral border.
• It directly stimulates Na⁺-H⁺ countertransport at the luminal border.

Bicarbonate Reabsorption in the Kidneys

Question: Explain the mechanism and site of reabsorption of filtered bicarbonate by the kidneys.

Answer:

This process occurs in the proximal convoluted tubule (PCT).

Bicarbonate in the lumen cannot diffuse readily into tubular cells. Thus, HCO₃^– ions are reabsorbed by a special process:

In the Lumen:

The luminal brush border of the PCT cell is the only one in renal tubules containing carbonic anhydrase (CA). H⁺ ions secreted into the PCT lumen by Na⁺-H⁺ exchange combine with filtered HCO₃^– in the presence of CA to form carbonic acid. Carbonic acid then is converted to CO₂ and H₂O, which diffuse into the PCT cell.

In the PCT Cells:

Intracellular CA catalyzes the reaction CO₂ and H₂O to form H₂CO₃, which then dissociates into H⁺ and HCO₃^–. H⁺ is secreted into the lumen via the Na⁺-H⁺ exchange mechanism in the luminal membrane, while HCO₃^– is reabsorbed via the basolateral membrane into the interstitium. The secreted H⁺ starts a new cycle.

Thus, each time an H⁺ ion is formed in tubular epithelial cells, an HCO₃^– ion is also formed and reabsorbed back into the blood. The result is net reabsorption of filtered HCO₃^–, but there is no net secretion of H⁺.

Hormones of Pregnancy

Question: Discuss the hormones secreted during the three trimesters of pregnancy, explaining their site of secretion and their actions.

Answer:

A. First Trimester (First 3 Months)

1. Corpus Luteum: The corpus luteum is responsible for the production of estrogen and progesterone.
2. Human Chorionic Gonadotropin (hCG): hCG is secreted from the placenta and reaches its peak levels at the 7th-9th gestational week, then decreases rapidly to reach low levels and remains low during the rest of pregnancy.

B. Second and Third Trimesters

1. Placenta: Estrogen and progesterone are produced by the placenta.
2. Human Placental Lactogen (hPL): hPL is produced by the placenta at the 5th week of pregnancy and remains throughout the pregnancy.

Functions of Pregnancy Hormones:

1. Human Chorionic Gonadotropin (hCG): hCG prevents degeneration of the corpus luteum and stimulates the secretion of estrogen and progesterone by the corpus luteum for the maintenance of pregnancy.
2. Estrogens:
   • Promote growth of the uterus and mammary glands.
   • Increase the number of oxytocin receptors in the uterus.
3. Progesterone:
   • Promotes the development of decidual cells needed for fetal nutrition.
   • Decreases uterine contractility during pregnancy.
   • Stimulates growth of breast alveoli.
4. Human Placental Lactogen (hPL): hPL is similar in function to both growth hormone (GH) and prolactin.
   • It mobilizes fat from fat stores and increases glucose production in the mother (GH effect).
   • It stimulates breast development in preparation for lactation (prolactin effect).

Both estrogen and progesterone suppress ovarian follicular growth and ovulation by inhibiting follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Functions of the Gallbladder

Question: Describe the functions of the gallbladder.

Answer:

1. Storage of Bile: Between meals, the sphincter of Oddi is closed, so bile flows to the relaxed gallbladder to be stored until needed.
2. Concentration of Bile: The volume of the gallbladder is 30-60 ml, but it can store up to 12 hours of bile secretion. This is due to the concentration of bile, which is caused by the absorption of water, NaCl, and bicarbonate.
3. Acidification of Bile: Due to the absorption of HCO₃^–, gallbladder bile becomes more acidic.

Evacuation of the Gallbladder:

This occurs by the contraction of the gallbladder and the relaxation of the sphincter of Oddi.

Control of Gallbladder Evacuation:

1. Cholecystokinin (CCK): The most important stimulus for gallbladder evacuation.
2. Vagal Stimulation

Factors Affecting Airway Diameter

Question: What factors affect the diameter of airways?

Answer:

A. Physical Factors

1. Intrapleural Pressure: The negative intrapleural pressure (Ppl) is the major factor keeping small airways (no cartilage) open. It distends them just as it distends alveoli.
   • With Inspiration: Ppl becomes more negative, which distends airways more, increasing airway radius and decreasing airway resistance.
   • With Expiration: The opposite occurs, increasing airway resistance.
2. Lateral Traction: Small airways have attachments to the walls of alveoli. As the alveoli expand during deep inspiration, the elastic recoil in their walls increases and is transmitted to the attachments of the airways, pulling them open and decreasing airway resistance. Thus, airway resistance decreases during inspiration and increases during expiration.

B. Nervous Factors

1. Vagus Nerve (Cholinergic) Stimulation: Causes bronchoconstriction and increased mucus secretion, increasing airway resistance.
2. β₂ Adrenergic Stimulation: Causes bronchodilation.

C. Chemical Factors

Many chemical substances contract bronchial smooth muscle, increasing airway resistance. Examples include:

• Histamine: Released from mast cells during allergic responses.
• Leukotrienes: Produced in the lungs in response to inflammation.
• Various Environmental Factors

Transport of Carbon Dioxide in Venous Blood

Question: Explain how carbon dioxide is transported in venous blood.

Answer:

CO₂ is generated in tissues and diffuses freely into venous blood and then into red blood cells (RBCs).

In RBCs, CO₂ combines with H₂O to form carbonic acid, a reaction catalyzed by the enzyme carbonic anhydrase. H₂CO₃ then dissociates into H⁺ and HCO₃^–.

HCO₃^– leaves the RBCs in exchange for Cl^– (chloride shift) and is transported to the lungs in the blood. H⁺ is buffered inside RBCs by deoxyhemoglobin.

Formation of Dilute Urine

Question: Describe the processes occurring in each segment of the renal tubules when the kidney produces dilute urine.

Answer:

Proximal Convoluted Tubule (PCT):

• Two-thirds of the filtered water is reabsorbed isosmotically.
• Water moves passively out of the PCT secondary to the active transport of solutes (obligatory water reabsorption).
• The osmolarity of fluid reaching the loop of Henle is approximately 300 mOsm/L.

Thin Descending Limb of Loop of Henle:

• It is permeable to water and less permeable to solutes.
• Water is reabsorbed by osmosis, and tubular fluid reaches equilibrium with the surrounding interstitial fluid of the renal medulla.
• Tubular fluid becomes more concentrated as it flows into the inner medulla.

Ascending Limb of Loop of Henle and Early DCT:

• They are called the diluting segments as they are impermeable to water.
• They reabsorb NaCl by the Na⁺-K⁺-2Cl^– cotransporter.
• Tubular fluid becomes hyposmotic (100 mOsm/L) as it reaches the late DCT.

Late DCT and Collecting Ducts (CDs):

• There is additional reabsorption of solutes, especially NaCl.
• In the absence of antidiuretic hormone (ADH), this portion of the tubule is impermeable to water.
• Tubular fluid becomes even more dilute, and its osmolarity is as low as 50 mOsm/L.
• The failure to reabsorb water and the continuous reabsorption of solutes lead to a large volume of dilute urine.

Functions of the Proximal Convoluted Tubule

Question: Describe the functions of the proximal convoluted tubule of the renal nephron.

Answer:

Reabsorption:

1. About 67% (2/3) of the filtered tubular load of Na⁺, Cl^–, HCO₃^–, K⁺, and water is reabsorbed.
2. Complete reabsorption of glucose and amino acids occurs by cotransport with Na⁺.
3. Partial reabsorption of urea occurs by diffusion, as its concentration increases in tubular fluid due to the reabsorption of water.
4. Obligatory Water Reabsorption: In the PCT, the reabsorption of solutes causes the reabsorption of an equal amount of H₂O. This process is isoosmotic, and the total osmolality of the tubular fluid remains unaffected (300 mOsm/L).

Secretion:

1. H⁺ ion secretion occurs by Na⁺-H⁺ countertransport.
2. Organic substances, such as bile salts, urates, oxalates, and catecholamines, are secreted.
3. Drugs, such as penicillin, salicylates, and para-aminohippuric acid (PAH), are secreted.

Hypothalamic-Pituitary Axis and Prolactin Regulation

Question: Describe the connection between the anterior pituitary and hypothalamus. Explain the hypothalamic regulation of prolactin and two actions of prolactin.

Answer:

Hypothalamic-Pituitary Connection:

The portal vessels connect the primary capillary plexus in the hypothalamus with the secondary capillary plexus in the anterior pituitary. Hypothalamic neurons secrete releasing and inhibitory hormones. These hormones are carried by the portal vessels from the hypothalamus to the anterior pituitary, thus regulating the secretion of anterior pituitary hormones.

Hypothalamic Regulation of Prolactin:

Prolactin (PRL) secretion is inhibited by prolactin-inhibiting hormone (PIH), which is dopamine, secreted by the hypothalamus. Thyrotropin-releasing hormone (TRH) stimulates prolactin secretion. However, the inhibitory effect of dopamine dominates and overrides the stimulatory effect of TRH.

Actions of Prolactin:

1. Milk Production: Prolactin stimulates milk production in the breast. It induces the synthesis of lactose (the carbohydrate of milk), casein (the protein of milk), and lipids. It also stimulates the secretion of fluids and electrolytes by the breast.
2. Breast Development: Prolactin, along with estrogen, stimulates breast development during pregnancy.

Actions of Oxytocin

Question: Describe the actions of oxytocin.

Answer:

1. Milk Ejection: Oxytocin stimulates the contraction of the myoepithelial cells of the breast, so milk is forced out from the mammary alveoli into the ducts and delivered to the baby.
2. Uterine Contractions:
   • During pregnancy, oxytocin receptors in the uterus are upregulated as labor approaches.
   • During labor, dilation of the cervix leads to marked secretion of oxytocin, resulting in more forceful uterine contractions (positive feedback loop). This leads to the expulsion of the baby.
3. Function in Males: Oxytocin causes contraction of the vas deferens and propelling of sperm into the urethra.

Ovarian Changes During the Early Follicular Phase

Question: Describe the ovarian changes during the first week of the follicular phase of the menstrual cycle. Explain the mechanism of estrogen formation by the growing follicles.

Answer:

Follicular Phase:

The follicular phase lasts from day 0 until day 14 of the menstrual cycle. The variability in the length of the cycle is attributable to variability in the duration of this phase.

Ovarian Changes During the First Week:

1. Follicle Recruitment: Due to increased levels of FSH and, to a lesser extent, LH secreted from the anterior pituitary, 10-15 primordial follicles start growing. This occurs by the enlargement of the ovum itself 2-3 times with the proliferation of granulosa cells (primary follicle).
2. Follicle Development:
   • Granulosa cells secrete a glycoprotein material called the zona pellucida.
   • Stromal cells develop around granulosa cells and are called theca cells. The theca cells divide into the secretory theca interna and an outer rim of fibrous tissue called the theca externa (preantral follicles).
   • Granulosa cells contain FSH receptors, and theca interna cells contain LH receptors.
3. Follicle Maturation: Increased FSH and LH lead to the multiplication of granulosa and theca cells, so the follicles increase in size, and fluid collects between granulosa cells, forming a large cavity filled with fluid called the antrum (antral follicles).

Estrogen Formation by the Growing Follicles:

LH stimulates theca interna cells to produce androgens, and in the presence of FSH, these androgens are converted by granulosa cells to estrogens, which accumulate in the antral fluid or are secreted into the blood.

Buffering of Hydrogen Ions in Renal Tubules

Question: Describe the buffering of hydrogen ions in renal tubular fluid in the proximal tubule as well as in the late distal tubules and collecting ducts.

Answer:

Proximal Convoluted Tubule (PCT):

In the Lumen:

In the presence of carbonic anhydrase (CA), secreted H⁺ and filtered HCO₃^– form carbonic acid, which then is converted to CO₂ and H₂O, which diffuse into the PCT cell.

In the PCT Cells:

In the presence of CA, CO₂ and H₂O form H₂CO₃, which then dissociates into H⁺ and HCO₃^–. H⁺ is secreted into the lumen via the Na⁺-H⁺ exchange mechanism in the luminal membrane, while HCO₃^– is reabsorbed via the basolateral membrane into the interstitium. The secreted H⁺ starts a new cycle.

Thus, each time an H⁺ ion is formed in tubular epithelial cells, an HCO₃^– ion is also formed and reabsorbed back into the blood. The result is net reabsorption of filtered HCO₃^–, but there is no net secretion of H⁺.

Late Distal Tubules and Collecting Ducts:

1. Excretion of H⁺ as Titratable Acid (H₂PO₄^–):
   • In Tubular Cells: H⁺ and HCO₃^– are produced in the cell from CO₂ and H₂O. The H⁺ is secreted into the lumen, and the HCO₃^– is reabsorbed into the blood (“new” HCO₃^–).
   • In the Tubular Lumen: The secreted H⁺ combines with filtered HPO₄^2- to form H₂PO₄^–, which is excreted as titratable acid.

   This process results in the net secretion of H⁺ and the net reabsorption of newly formed HCO₃^–. As a result of H⁺ secretion, the pH of urine becomes progressively lower.

2. Excretion of H⁺ as Ammonium (NH₄⁺):
   • In Tubular Cells: NH₃ (ammonia) is produced by renal cells from glutamine. It diffuses down its concentration gradient from the cells into the lumen. H⁺ and HCO₃^– are produced from CO₂ and H₂O. The H⁺ ion is secreted into the lumen, while the HCO₃^– ion is reabsorbed into the blood (“new” HCO₃^–).
   • In the Lumen: H⁺ combines with NH₃ to form NH₄⁺, which is excreted. This process also results in the net secretion of H⁺ and the net reabsorption of newly synthesized HCO₃^–.

Autoregulation of Glomerular Filtration Rate

Question: Explain how autoregulation helps maintain a constant glomerular filtration rate (GFR).

Answer:

Autoregulation keeps the GFR constant over a range of arterial blood pressure (ABP) from 80 to 200 mmHg by changing renal vascular resistance.

1. Myogenic Autoregulation: Renal arterioles contract in response to stretch. Thus, decreased ABP reduces stretch on the arterioles, which relax, decreasing vascular resistance and preventing a decrease in GFR during decreased ABP. Conversely, increased ABP increases stretch, causing arteriole constriction, increasing resistance, and preventing an increase in GFR.
2. Tubuloglomerular Feedback: This is a feedback mechanism that buffers the effect of changes in ABP on GFR:
   • Increased ABP leads to increased GFR and a faster rate of flow of tubular fluid in renal tubules.
   • This leads to decreased NaCl reabsorption in the loop of Henle and an increased NaCl concentration in the tubular fluid reaching the DCT.
   • This initiates a signal in the macula densa that has two effects:
     1. Vasoconstriction of the Afferent Arteriole: This decreases glomerular capillary pressure (PGC), decreasing GFR toward normal.
     2. Vasoconstriction of the Efferent Arteriole (Indirectly): This occurs via decreased renin release by juxtaglomerular cells, leading to less angiotensin II formation. Reduced angiotensin II leads to vasodilation of the efferent arteriole, increasing PGC and preventing a decrease in GFR during increased ABP.