Renal Function, Digestion, and Thyroid Hormone Actions
Mechanisms of Dilute Urine Formation
Occurs in situations of overhydration.
Proximal Tubule
Water reabsorption is proportional to solute reabsorption. The tubular fluid remains isosmotic to plasma (osmolarity is constant).
Descending Loop of Henle
The renal medulla is hyperosmolar, increasing in concentration deeper towards the renal papillae. Water moves out into the hyperosmolar interstitium. Solutes are not reabsorbed. Intratubular osmolarity increases.
Ascending Loop of Henle
This segment is impermeable to water. Solutes (NaCl) are actively reabsorbed, decreasing the intratubular osmolarity.
Collecting Duct
In the absence of Antidiuretic Hormone (ADH), aquaporin-2 channels are not inserted into the apical membrane. The collecting duct is impermeable to water. Water remains in the tubule, and the final urine becomes very dilute as solutes may continue to be reabsorbed. Osmolarity decreases further.
Mechanisms of Concentrated Urine Formation
Occurs in situations of dehydration (hypovolemia).
In dehydration, humans can form urine with an osmolarity up to 1200 mOsm/L or slightly more. The ability to concentrate urine increases with adaptation to dehydration. Two conditions are necessary:
- High circulating levels of ADH.
- A significant medullary hyperosmotic gradient.
Phases
Proximal Tubule
Isosmotic reabsorption occurs, similar to dilute urine formation.
Descending Loop of Henle
Water moves out into the hyperosmolar interstitium, concentrating the tubular fluid.
Ascending Loop of Henle
Solutes are reabsorbed, but this segment remains impermeable to water. Urea recycling contributes to the medullary gradient.
Collecting Duct
With high ADH levels, the late distal tubule and collecting duct become permeable to water. Water is reabsorbed into the hyperosmolar interstitium, concentrating the urine. In the medullary collecting duct, ADH also increases urea permeability, allowing urea reabsorption, which further contributes to the medullary hyperosmolarity.
Role of Vasa Recta
Features
The medulla is relatively poorly vascularized. The vasa recta are straight capillaries arising from efferent arterioles of juxtamedullary nephrons. As they descend into the hyperosmolar medulla, they lose water and gain solutes. As they ascend back towards the cortex, they gain water and lose solutes.
Function
This countercurrent exchange mechanism allows the vasa recta to supply blood to the medulla without washing out the hyperosmotic gradient.
Location
Vasa recta are found only in the renal medulla.
Early Digestive Processes
Carbohydrate Digestion
Process
- Digestion begins in the mouth with salivary amylase (ptyalin), which breaks down 20-40% of ingested starch.
- Pancreatic amylase in the small intestine breaks down the remaining starch (50-80%).
- The main products reaching the small intestine are disaccharides: maltose (from starch), lactose (from milk), and sucrose (table sugar).
- These disaccharides are hydrolyzed into monosaccharides by enzymes (maltase, lactase, sucrase) located in the brush border of enterocytes before or during absorption.
Protein Digestion
Process
Stomach
Pepsinogen is secreted and activated to pepsin by the low pH created by HCl. Pepsin begins protein digestion, breaking down 10-20% of ingested proteins, particularly collagen.
Pancreas
Secretes several proteolytic enzymes as inactive proenzymes (e.g., trypsinogen, chymotrypsinogen). Enterokinase, an enzyme in the intestinal brush border, activates trypsinogen to trypsin, which then activates other pancreatic proenzymes.
Intestine
Enterocytes contain peptidases in their brush border and cytoplasm that further break down small peptides into amino acids for absorption.
Fat Digestion
Process
Mouth/Stomach
Lingual lipase (from glands in the tongue) and gastric lipase initiate fat digestion, but their contribution is limited in adults.
Small Intestine (Bile)
Bile, produced by the liver and stored in the gallbladder, emulsifies large fat globules into smaller droplets. This increases the surface area for enzyme action significantly. Bile salts stabilize these droplets and form micelles.
Enzymes
Pancreatic lipase is the primary enzyme for fat digestion, breaking down triglycerides into fatty acids and monoglycerides after emulsification.
Absorption
Fatty acids and monoglycerides, along with other lipids, are transported within micelles to the surface of enterocytes for absorption. Inside the enterocytes, triglycerides are re-synthesized, packaged into chylomicrons, and secreted into the lymphatic system. Bile salts are reabsorbed in the ileum and returned to the liver (enterohepatic circulation).
Thyroid Hormone Effects
General Effects
- Increase the number and size of mitochondria.
- Increase the activity of the Na+/K+-ATPase pump.
- Stimulate overall metabolic activity, increasing oxygen consumption and heat production (calorigenic effect).
- Promote normal growth and development, particularly of the nervous system and skeleton.
Specific Effects
- Carbohydrate Metabolism: Stimulate glucose absorption from the gut and increase gluconeogenesis and glycogenolysis.
- Fat Metabolism: Stimulate lipolysis (fat breakdown) and increase fatty acid oxidation.
- Plasma Lipids: Decrease plasma concentrations of cholesterol, phospholipids, and triglycerides by increasing their clearance (e.g., promoting LDL receptor formation in the liver).
- Vitamins: Increase the requirement for vitamins due to increased metabolic rate.
- Basal Metabolic Rate (BMR): Increase BMR in almost all tissues.
- Body Weight: Tend to decrease body weight due to increased catabolism (if caloric intake doesn’t increase).
- Cardiovascular System: Increase heart rate, cardiac output, and blood flow to tissues.
- Respiratory System: Increase respiration rate and depth to meet increased oxygen demand.
- Digestive System: Increase appetite and food intake, increase gut motility and secretion.
- Central Nervous System (CNS): Essential for normal CNS development and function. Affect mental alertness and reflexes.
- Muscles: Affect muscle function; excess can cause muscle weakness or tremor, deficiency can cause sluggishness.
- Sleep: Imbalances can cause sleep disturbances (hyperthyroidism: insomnia; hypothyroidism: somnolence).
- Other Endocrine Glands: Influence the secretion and metabolism of other hormones.
- Sexual Function: Normal thyroid hormone levels are necessary for normal sexual function in both males and females.
- Bone Growth: Promote normal bone growth and maturation, acting synergistically with growth hormone.