Renal Physiology: Body Water Balance

• Renal Physiology & Water Balance is part of Structural and Functional Biology

Body Water

• About 60% of total body weight is water
• The fluids in the body are either extracellular fluid (ECF) or intracellular fluid (ICF)
• Extracellular fluid (ECF) makes up approximately 20% of body weight, and includes plasma (intravascular), interstitial fluid, and transcellular water
• Intracellular fluid (ICF) makes up approximately 40% of body weight

Extracellular Fluid Details

• A small portion (~1%) of ECF is considered "transcellular water"
• Transcellular water is localized in specific areas. Examples:
  • Lymph in lymphatic vessels
  • Cerebrospinal fluid in the brain
  • Synovial fluid in joints
  • Aqueous humor and vitreous body in the eyes
  • Endolymph and perilymph in the ears
  • Pleural, pericardial and peritoneal fluids between serous membranes
  • Glomerular filtrate in the kidneys

Water Balance Factors:

• Water intake is influenced by:
  • Ingested liquid (drinking water)
  • Ingested food
  • Metabolic water (water of oxidation)
• Water losses occur via:
  • Urine
  • Skin (sweat)
  • Lungs (exhaled water vapor)
  • Gastrointestinal tract (feces)

Kidney Overview

• Kidneys maintain extracellular fluid composition within defined limits, to allow cells to survive
• The kidneys primarily stabilize the volume and ion concentrations of the extracellular fluid
• Kidneys enable mammals to survive in conditions of highly variable access to water and salts
• The anatomy of the Urinary System has these components: the kidneys, ureters, urinary bladder, and urethra

Kidney Functions

• The kidney is of primary physiological relevance. Kidney functions include:
  • Urine production
  • Blood filtration
  • Metabolic waste & xenobiotic excretion
  • Retrieval of needed metabolic substances: Water, glucose, electrolytes, Low MW proteins
  • Responding to water, electrolyte and acid-base disturbances
  • Gluconeogenesis (Glucose production)
  • Hormone production associated with systemic blood pressure, red blood cell production & calcium metabolism

Endocrine Functions of the Kidney

• Kidneys produce and secrete hormones into circulation
  • Calcitriol (1,25-(OH)2-D3) is stimulated by PTH in response to hypocalcemia
  • Renin: hormone activator, renal regulation of blood pressure, essential part of the renin-angiotensin-aldosterone system (RAA system)
  • Erythropoietin: hormone (glycoprotein, growth factor), is essential for erythropoiesis

The Nephron

• The nephron is the functional unit of the kidney
  • In humans: ~1 million per kidney
  • In cows: ~4 million
  • In dogs: 400,000
  • In cats: 190,000
• Nephrons cannot be replaced, and are only partially regenerated
• Kidneys contain two types of nephrons differing in location and capillary networks: cortical and juxtamedullary

Cortical Nephrons

• Glomerulus is located far from the cortex/medulla junction
• Short loops of Henle
• Blood supply by peritubular capillaries

Juxtamedullary Nephrons

• Glomerulus is located near the cortex/medulla junction
• Efferent arterioles give rise to long straight capillaries (vasa recta) that descend into the renal medulla
• Have long Loops of Henle (critical for urine concentration)

Structures of the Nephron

• Renal Corpuscle(Malpighian body) is located in the renal cortex:
  • Glomerulus (capillaries)
  • Bowman's capsule (double-walled capsule)
• Proximal tubule is the longest part of the nephron (~10 mm): proximal convoluted (PCT) and straight part (PST)
• The loop of Henle: thick descending limb (extending into the renal medulla), a thin descending limb, a thin ascending limb (ONLY in nephrons which have long loops!), and a thick ascending limb (TAL, macula densa!)
• The distal tubule: convoluted part (DCT) and straight (DST)
• The collecting ducts (CD): extend through the renal cortex and medulla

Structures of the Nephron location

• At the renal papilla, CD open in the renal pelvis -> via ureter -> urinary bladder -> urethra -> exit

Glomerular Filtration

• It is the first step in urine formation
• Large amounts of fluid pass through glomerular capillaries into Bowman's capsule
• The glomerulus: compact network of capillaries that retains cellular components and proteins, has semipermiable membrane
• Most of the filtration (99%+) is reabsorbed, so leaving less than 1 liter to be excreted (highly variable)
• Adult dogs produce ~20 to 40 ml of urine per kilogram of body weight per 24 hours (1.0 to 2.0 ml/kg/hour)
• Adult cats produce an average of 28 ml of urine per kilogram of body weight per 24 hours (~1.2 ml/kg/hr)
• GFR = 2.4 – 3.7 mL/min/kg, and Up to 5,328 mL/kg/day

Primary Urine Factors

• The ultra filtrate accumulates in the capsular space between glomerulus and Bowman's capsule (Bowman's space)
• Primary urine contains the same concentration of salt and glucose as plasma
• Tubular fluid: filtrate inside the tubular system
• In passage through the system, the tubular fluid gets modified by tubular reabsorption and becomes "final urine"
• Tubular reabsorption recovers most filtered substances, like Glucose (100%), H2O (99%), Na+, Ca++, Cl-, HCO3-

Glomerular Filterability

• It depends on molecular weight
• Electrolytes (sodium) and small organic compounds (glucose) are filtered as freely as water

Factors affecting Glomerular Selective Filtration

• Electrical charge: Cationic (+) substances are more easily filtered than anionic (-) substances. This is due to the negative charge of the glomerular basement membrane
• Plasma protein binding: Protective mechanism for some solutes, such as calcium. Some drugs retained in the circulation for a defined time period before elimination

Osmolality

• Osmolality is the number of osmoles of solute per kilogram of solvent
• Because volume is temperature-dependent, osmolality is more suitable in living organisms (Osm/Kg water)

Fluid Movement

• Two forces contributing to fluid movement: hydrostatic/hydraulic pressure and osmotic or oncotic pressure
• Glomerulus filtration adds a third factor, the permeability of the capillary membranes in the glomerulus

Glomerular Capillary Hydrostatic Pressure

• The main driving force for filtration is the glomerular capillary hydrostatic pressure
• Opposing forces are the hydrostatic pressure in Bowman's space and the oncotic pressure of the blood plasma
• The oncotic pressure of the filtrate is essentially non-existent

Water Balance & Kidney Functions

• An important function of the kidney is to maintain the water content of the body and plasma tonicity (extracellular osmolality)
• Terrestrial animals face the challenge of dehydration
• Water reabsorption in the kidney is therefore extremely important
• Reabsorption of water by the renal tubules is used to maintain water in the body, producing a concentrated urine
• The advantage of urine concentration is reduced water requirements

Water Reabsorption in Kidneys

• PT reabsorbs water through aquaporins (AQP's) and solute reabsorption
• Sodium reabsorption encourages water movement into the cells and into the interstitium
• The thin descending limb of Henle's loop reabsorbs water by osmosis
• The collecting ducts are adjustable by ADH-sensitive AQP's

Medullary Segments and Urine Concentration

• If osmolality in plasma is increased ADH release → production of concentrated urine
• Water deficit increases extracellular osmolarity which activates osmoreceptors in the hypothalamus gland
• The production of ADH from the pituitary gland then increases water permeability in the Collecting Ducts

ADH and Osmolality

• CD is water permeable and determines excreted urine osmolality
• In ADH absence, CD is relatively impermeable to water
• A result is the production of diluted urine