BIO 202 Renal I and II Anatomy and Physiology II Flashcards

Introduction to the Urinary System

• The urinary system is crucial for removing waste products from the body.

• It also plays key roles in regulating blood volume, pressure, and composition.

• The urinary system is closely linked to the reproductive system through shared embryonic development and anatomical relationships, collectively termed the urogenital (UG) system.

Anatomy of the Urinary System

• Key structures include:

  • Kidneys

  • Ureters

  • Urinary bladder

  • Urethra

• Associated structures:

  • Adrenal glands

  • Inferior vena cava

  • Aorta

  • Iliac crest

  • Rectum (cut)

  • Uterus (in females)

Important Review Concepts

• Solute: A substance that is dissolved in a solution.

• Solvent: The liquid in which a solute is dissolved.

• Osmolarity: The total concentration of all solutes in a solution.

• Plasma: The water component of blood, serving as the solvent.

• Filtrate: The portion of plasma that is filtered by the kidney.

• Urine: The final substance produced after the kidney processes the filtrate.

Composition of Blood Plasma, Glomerular Filtrate, and Urine

• Key substances and their average amounts in blood plasma, glomerular filtrate, and urine are:

  • Water: Glomerular Filtrate - 180 L/day, Urine - 1-2 L/day

  • Urea: Blood Plasma - 3 L, Glomerular Filtrate - 53 g, Urine - 25 g

  • Chloride: Blood Plasma - 639 g, Urine - 4.8 g

  • Sodium: Blood Plasma - 580 g, Urine - 10.7 g

  • Potassium: Blood Plasma - 30 g, Urine - 0.5 g

  • Creatinine: Blood Plasma - 1.6 g, Urine - 1.6 g

  • Uric acid: Blood Plasma - 8.5 g, Urine - 0.03 g

  • Protein: Blood Plasma - 0.1 g, Urine - 200 g

  • Bicarbonate: Blood Plasma - 275 g, Urine - 4.69 g

  • Glucose: Blood Plasma - 180 g, Urine - 3 g

Functions of the Kidneys

• Filter blood plasma and excrete toxic wastes.

• Regulate blood volume, pressure, and osmolarity.

• Regulate electrolytes and acid-base balance.

• Secrete erythropoietin, which stimulates the production of red blood cells.

• Help regulate calcium levels by participating in calcitriol synthesis.

• Clear hormones from the blood.

• Detoxify free radicals.

• Synthesize glucose from amino acids during starvation.

Nitrogenous Wastes

• Waste: Any substance that is useless to the body or present in excess.

• Metabolic waste: Waste substances produced by the body.

• Urea formation: Proteins are broken down into amino acids, then NH_2 is removed, forming ammonia, which the liver converts to urea.

• Uric acid: A product of nucleic acid catabolism.

• Creatinine: A product of creatine phosphate catabolism.

Blood Urea Nitrogen (BUN)

• BUN measures the level of nitrogenous waste in the blood.

• The normal concentration of blood urea is 10 to 20 mg/dL.

• Azotemia: Elevated BUN, may indicate renal insufficiency.

• Uremia: A syndrome of diarrhea, vomiting, dyspnea, and cardiac arrhythmia, stemming from the toxicity of nitrogenous waste.

• Treatment for uremia includes hemodialysis or organ transplant.

Excretion

• Excretion involves separating wastes from body fluids and eliminating them.

• Four body systems carry out excretion:

  • Urinary system: Excretes many metabolic wastes, toxins, drugs, hormones, salts, H^+, and water.

  • Respiratory system: Excretes CO_2, small amounts of other gases, and water.

  • Digestive system: Excretes water, salts, CO_2, lipids, bile pigments, cholesterol, and other metabolic wastes.

  • Integumentary system: Excretes water, inorganic salts, lactic acid, and urea in sweat (though normally not significant in terms of fluid excretion in humans)

Kidney Position and Associated Structures

• Kidneys lie against the posterior abdominal wall at the level of T12 to L3.

• The right kidney is slightly lower due to the large right lobe of the liver.

• Rib 12 crosses the middle of the left kidney.

• The kidneys are retroperitoneal, along with the ureters, urinary bladder, renal artery and vein, and adrenal glands.

Gross Anatomy of the Kidney

• Key structures include:

  • Fibrous capsule

  • Renal cortex

  • Renal medulla

  • Renal pelvis

  • Major calyx

  • Minor calyx

  • Ureter

  • Renal papilla

  • Renal sinus

  • Renal column

  • Renal pyramid

Renal Circulation

• The kidneys make up only 0.4% of body weight but receive about 21% of cardiac output.

  • ~1 liter/min = 60 liters/hour = 1440 liters/day

  • Filtrate ~ 180 liters/day

  • Approximately 12.5% (180/1440) of renal blood flow gets filtered.

• The renal artery divides into segmental arteries, which give rise to:

  • Interlobar arteries: run up renal columns between pyramids

  • Arcuate arteries: run over pyramids

  • Cortical radiate arteries: run up into the cortex

  • Afferent arterioles: branch off cortical radiate arteries, each supplying one nephron

• The afferent arterioles lead to the glomerulus, a ball of capillaries.

Renal Circulation (Continued)

• Blood drains from the glomerulus via efferent arterioles.

• Most efferent arterioles lead to peritubular capillaries.

• Some efferent arterioles lead to vasa recta, a network of blood vessels within the renal medulla.

• Capillaries then lead to cortical radiate veins or directly into arcuate veins.

• Arcuate veins lead to interlobar veins, which lead to the renal vein.

• The renal vein empties into the inferior vena cava.

Renal Circulation in Cortex and Medulla

• In the cortex, peritubular capillaries branch off the efferent arterioles, supplying tissue near the glomerulus and the proximal and distal convoluted tubules.

• In the medulla, the efferent arterioles give rise to the vasa recta, supplying the nephron loop portion of the nephron.

The Nephron

• Each kidney contains about 1.2 million nephrons.

• Each nephron consists of two principal parts:

  • Renal corpuscle (glomerulus): filters the blood plasma

  • Renal tubule: a long, coiled tube that converts the filtrate into urine (proximal tubule, loop, distal tubule)

• The renal corpuscle consists of the glomerulus and a two-layered glomerular capsule that encloses the glomerulus.

  • The parietal (outer) layer of the glomerular capsule is simple squamous epithelium.

  • The visceral (inner) layer consists of podocytes that wrap around the capillaries of the glomerulus.

• The capsular space separates the two layers of the glomerular capsule.

The Renal Corpuscle

• Glomerular filtrate collects in the capsular space and flows into the proximal convoluted tubule.

• Vascular pole: The side of the corpuscle where the afferent arteriole enters and the efferent arteriole leaves.

• Urinary pole: The opposite side of the corpuscle where the renal tubule begins.

The Renal Tubule

• The renal (uriniferous) tubule is the portion of the nephron leading away from the glomerular capsule.

• It is divided into three regions:

  • Proximal convoluted tubule

  • Nephron loop

  • Distal convoluted tubule

• Proximal convoluted tubule (PCT): Arises from the glomerular capsule, is the longest and most coiled region, and is lined with simple cuboidal epithelium with prominent microvilli for absorption.

The Renal Tubule (Continued)

• Nephron loop: A long U-shaped portion of the renal tubule, consisting of a descending limb and an ascending limb.

  • Thick segments have simple cuboidal epithelium and are heavily engaged in the active transport of salts, containing many mitochondria; these form the initial part of the descending limb and part or all of the ascending limb.

  • Thin segments have simple squamous epithelium, forming the lower part of the descending limb, and are very permeable to water.

• Distal convoluted tubule (DCT): Begins shortly after the ascending limb reenters the cortex, is shorter and less coiled than the PCT, and is lined with cuboidal epithelium without microvilli; it is the end of the nephron.

Collecting Duct

• The collecting duct is contiguous with the renal tubule anatomically but represents a different functional component, acting to conserve water (concentrate urine) under the influence of ADH; it receives fluid from the DCTs of several nephrons as it passes back into the medulla.

• Numerous collecting ducts converge toward the tip of the medullary pyramid.

• Papillary duct: Formed by the merger of several collecting ducts; 30 papillary ducts end in the tip of each papilla.

• Collecting and papillary ducts are lined with simple cuboidal epithelium.

• The process of converting filtrate to urine is complete when it is in the papillary duct.

Flow from Plasma to Filtrate to Urine

• The flow of fluid from the point where the glomerular filtrate is formed to the point where urine leaves the body:

  • Afferent arteriole (plasma) → glomerular capsule (filtrate) → proximal convoluted tubule → nephron loop → distal convoluted tubule → collecting duct → papillary duct (urine) → minor calyx → major calyx → renal pelvis → ureter → urinary bladder → urethra

Basic Stages of Urine Formation

• The kidneys convert blood plasma to urine in four stages:

  • Glomerular filtration: Creates a plasmalike filtrate of the blood.

  • Tubular reabsorption: Removes useful solutes from the filtrate and returns them to the blood (mainly in PCT).

  • Tubular secretion: Removes additional wastes from the blood and adds them to the filtrate (mainly in DCT).

  • Water conservation: Removes water from the urine and returns it to the blood, concentrating wastes (mainly in the collecting duct, influenced by ADH, and some in the nephron loop with the salinity gradient).

Urine Formation: Glomerular Filtration

• Glomerular filtrate: The fluid in the capsular space, similar to blood plasma except that it has almost no protein.

• Tubular fluid: Fluid from the proximal convoluted tubule through the distal convoluted tubule, where substances have been removed or added by tubular cells.

• Urine: Fluid that enters the collecting duct, undergoing little alteration beyond this point except for changes in water content.

The Filtration Membrane

• Almost any molecule smaller than 3 nm can pass freely through the filtration membrane, including water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes, and vitamins.

• Some substances of low molecular weight are bound to plasma proteins and cannot get through the membrane, such as most calcium, iron, and thyroid hormone; the unbound fraction passes freely into the filtrate.

The Filtration Membrane and Kidney Damage

• Kidney infections and trauma can damage the filtration membrane, allowing albumin or blood cells to filter.

• Proteinuria (albuminuria): Presence of protein in urine.

• Hematuria: Presence of blood in the urine.

• Distance runners and swimmers often experience temporary proteinuria or hematuria due to prolonged, strenuous exercise reducing perfusion of the kidney and causing the glomerulus to deteriorate under prolonged hypoxia.

Filtration Pressure

• Filtration pressure depends on hydrostatic and osmotic pressures on each side of the filtration membrane.

• Blood hydrostatic pressure (BHP): High in glomerular capillaries (60 mm Hg compared to 10 to 15 in most other capillaries) because the afferent arteriole is larger than the efferent arteriole.

• Hydrostatic pressure in capsular space: 18 mm Hg due to high filtration rate and continual accumulation of fluid in the capsule.

Forces Involved in Glomerular Filtration

• High blood pressure in the glomerulus makes the kidneys vulnerable to hypertension.

• Hypertension can lead to rupture of glomerular capillaries, scarring of the kidneys (nephrosclerosis), and atherosclerosis of renal blood vessels, ultimately leading to renal failure.

• Net Filtration Pressure (NFP) : NFP = BHP - COP - CP. Where: Blood hydrostatic pressure (BHP) = 60 mm Hg (out), Colloid osmotic pressure (COP) = -32 mm Hg (in), Capsular pressure (CP) = -18 mm Hg (in), NFP = 10 mm Hg (out)

Sympathetic Control

• Sympathetic nerve fibers richly innervate the renal blood vessels.

• The sympathetic nervous system and adrenal epinephrine constrict the afferent arterioles during strenuous exercise or acute conditions like circulatory shock, reducing GFR and urine output.

• This redirects blood from the kidneys to the heart, brain, and skeletal muscles.

• GFR may be as low as a few milliliters per minute.

Renin–Angiotensin–Aldosterone Mechanism

• The renin-angiotensin-aldosterone mechanism is a hormonal system that helps control blood pressure and GFR.

• In response to a drop in blood pressure, baroreceptors in the carotid and aorta stimulate the sympathetic nervous system.

• Sympathetic fibers trigger the release of renin by the kidneys' granular cells.

• Renin converts angiotensinogen, a blood protein, into angiotensin I.

Renin–Angiotensin–Aldosterone Mechanism (Continued)

• In the lungs and kidneys, angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II.

• Angiotensin II is an active hormone that increases BP.

  • It is a potent vasoconstrictor, raising BP throughout the body.

  • It constricts the efferent arteriole, raising GFR despite low BP.

  • It lowers BP in peritubular capillaries, enhancing reabsorption of NaCl and H_2O.

  • It stimulates the adrenal cortex to secrete aldosterone, which promotes Na^+ and H_2O reabsorption in the DCT and collecting duct.

  • It stimulates Na^+ and H_2O reabsorption in the PCT.

  • It stimulates the posterior pituitary to secrete ADH, which promotes water reabsorption by the collecting duct.

  • It stimulates thirst.

The Proximal Convoluted Tubule

• The PCT reabsorbs about 65% of the glomerular filtrate, removes some substances from the blood, and secretes them into the tubular fluid for disposal in urine.

• It has prominent microvilli and great length.

• Abundant mitochondria provide ATP for active transport.

• PCTs alone account for about 6% of one’s resting ATP and calorie consumption.

• Tubular reabsorption: The process of reclaiming water and solutes from the tubular fluid and returning them to the blood.

Tubular Reabsorption

• Each day, the kidneys reduce 180 L of glomerular filtrate to 1 or 2 L of urine.

• Two-thirds of the water in the filtrate is reabsorbed in the PCT.

• Reabsorption of solutes makes the tubule cells and tissue fluid hypertonic to the tubular fluid.

• Water follows solutes by osmosis through both paracellular and transcellular routes.

• Transcellularly, water uses channels called aquaporins.

• In the PCT, water is reabsorbed at a constant rate, termed obligatory water reabsorption.

Uptake by the Peritubular Capillaries

• Peritubular capillaries reabsorb water and solutes that leave the basal surface of the tubular epithelium.

• Reabsorption occurs by osmosis and solvent drag.

• Three factors promote osmosis into the capillaries:

  • High interstitial fluid pressure due to the accumulation of reabsorbed fluid in the extracellular space.

  • Low blood hydrostatic pressure in peritubular capillaries due to the narrowness of efferent arterioles.

  • High colloid osmotic pressure in blood due to the presence of proteins that were not filtered.

The Nephron Loop

• The primary function of the nephron loop is to generate a salinity gradient that enables the collecting duct to concentrate the urine and conserve water.

• Electrolyte reabsorption from filtrate:

  • The thick segment reabsorbs 25% of Na^+, K^+, and Cl^− in the filtrate.

  • Ions leave cells by active transport and diffusion.

  • NaCl remains in the tissue fluid of the renal medulla.

  • Water cannot follow since the thick segment is impermeable.

  • Tubular fluid is very dilute as it enters the distal convoluted tubule.

Loop of Henle

• In the descending limb the water potential of the fluid is decreased by the addition of mineral ions and the removal of water.

• In the ascending limb the water potential is increased as mineral ions are removed by active transport.

• Ascending limb is impermeable to water

The Distal Convoluted Tubule

• The DCT reabsorbs Na^+, Cl^−, and water under hormonal control, especially aldosterone and ANP, but mainly provides excretory function.

• The tubules also extract drugs, wastes, and some solutes from the blood and secrete them into the tubular fluid.

• The DCT continues the process of making urine.

• The collecting duct conserves water (concentrates urine) due to ADH.

Collecting Duct

• Concentrates urine by reabsorbing water.

• This is regulated primarily by ADH.

• As plasma osmolarity increases, more ADH is produced.

• Increased ADH stimulates increased water reabsorption, preventing further osmolarity increase.

• If plasma osmolarity decreases, ADH secretion stops, and water is excreted, thus raising plasma osmolarity.

Summary of Nephron Function

• PCT reabsorbs 65% of the glomerular filtrate and returns it to the peritubular capillaries; it is mainly the site for reabsorption.

• The nephron loop reabsorbs another 25% of the filtrate.

• The DCT mainly provides mainly excretory function.

• The collecting duct reabsorbs water (concentrates urine) under the influence of ADH.

Summary of Reabsorption and Secretion

• A comprehensive overview of what is reabsorbed and secreted in the PCT, nephron loop, DCT, and collecting duct, including water, ions, urea, glucose, amino acids, and other substances.

Composition and Properties of Urine

• Urinalysis: Examination of the physical and chemical properties of urine.

• Appearance: Varies from clear to deep amber depending on the state of hydration; yellow color is due to urochrome pigment from the breakdown of hemoglobin (RBCs); cloudiness or blood could suggest urinary tract infection, trauma, or stones, or might just be contamination with other fluids.

• Pyuria: Pus in the urine.

• Hematuria: Blood in the urine due to urinary tract infection, trauma, or kidney stones.

• Odor: Bacteria degrade urea to ammonia; some foods and diseases impart particular aromas.

Composition and Properties of Urine (Continued)

• Specific gravity: Compares a urine sample’s density to that of distilled water; ranges from 1.001 to 1.028 g/mL.

• Osmolarity: Ranges from 50 mOsm/L to 1,200 mOsm/L in a dehydrated person (blood=300 mOsm/L).

• pH: Range: 4.5 to 8.2, usually 6.0 (mildly acidic).

• Chemical composition: 95% water, 5% solutes.

  • Normal to find: urea, NaCl, KCl, creatinine, uric acid, phosphates, sulfates, traces of calcium, magnesium, and sometimes bicarbonate, urochrome, and a trace of bilirubin.

  • Abnormal to find: glucose, free hemoglobin, albumin, ketones, bile pigments.

Urine Volume

• Normal volume for an average adult: 1 to 2 L/day.

• Polyuria: Output in excess of 2 L/day.

• Oliguria: Output of less than 500 mL/day.

• Anuria: 0 to 100 mL/day.

  • Low output from kidney disease, dehydration, circulatory shock, prostate enlargement.

  • Low urine output of less than 400 mL/day means the body cannot maintain a safe, low concentration of waste in the plasma (leads to azotemia).

Urine Volume and Diuretics

• Diuretics: Any chemical that increases urine volume.

  • Some increase GFR (e.g., caffeine dilates the afferent arteriole).

  • Some reduce tubular reabsorption of water (e.g., alcohol inhibits ADH secretion).

  • Some act on the nephron loop (loop diuretic), inhibiting the Na^+–K^+–Cl^− symport, which impairs the countercurrent multiplier, reducing the osmotic gradient in the renal medulla, making the collecting duct unable to reabsorb as much water as usual.

• Diuretics are commonly used to treat hypertension and congestive heart failure by reducing the body’s fluid volume and blood pressure.

Glomerular Filtration Rate Measurement

• GFR is often measured to assess kidney disease.

• The clearance rate of urea cannot be used because reabsorption and secretion of urea influence its clearance.

• Inulin, a plant polysaccharide, is used to determine GFR because it is neither reabsorbed nor secreted by the renal tubule.

  • A known concentration of inulin can be injected into the blood, and its output in the urine can be measured (Inulin clearance = GFR).

• Clinically, GFR is estimated from creatinine excretion, which does not require injecting a substance and has a small, acceptable amount of error.

Urine Storage and Elimination

• Urine is produced continually but does not drain continually from the body.

• Urination is episodic, occurring when we allow it, made possible by storage apparatus and neural controls for timely release.

The Ureters

• Ureters are retroperitoneal, muscular tubes that extend from each kidney to the urinary bladder (about 25 cm long).

• They pass posterior to the bladder and enter it from below.

• A flap of mucosa at the entrance of each ureter acts as a valve into the bladder, preventing urine from backing up into the ureter when the bladder contracts.

The Urinary Bladder

• The urinary bladder is a muscular sac located on the floor of the pelvic cavity, inferior to the peritoneum and posterior to the pubic symphysis.

• It has three layers:

  • Covered by parietal peritoneum superiorly and by fibrous adventitia elsewhere.

  • Muscularis: detrusor (three layers of smooth muscle).

  • Mucosa: transitional epithelium, with umbrella cells on the surface protecting it from the hypertonic, acidic urine; rugae (conspicuous wrinkles in empty bladder).

The Urinary Bladder (Continued)

• Trigone: A smooth-surfaced triangular area on the bladder floor marked with openings of the ureters and urethra.

• Capacity: Moderate fullness is 500 mL, maximum fullness is 700 to 800 mL.

  • Highly distensible; as it fills, it expands superiorly, rugae flatten, and the epithelium thins from five or six layers to two or three.

Urinary Tract Infection (UTI)

• Cystitis: Infection of the urinary bladder, more common in females due to the short urethra and frequently triggered by sexual intercourse; can spread up the ureter causing pyelitis.

• Pyelitis: Infection of the renal pelvis.

• Pyelonephritis: Infection that reaches the cortex and the nephrons, can result from blood-borne bacteria.

Neural Control of Micturition

• Involuntary micturition reflex initiated by stretch receptors detecting filling of the bladder, transmitting afferent signals to the spinal cord.

• Voluntary control involves the micturition center in the pons receiving signals from stretch receptors, which can either excite spinal interneurons (if it is timely to urinate) or keep the external urethral sphincter contracted (if it is untimely to urinate).

Fluid Balance

• Cellular function requires a fluid medium with a carefully controlled composition.

• Three types of homeostatic balance:

  • Water balance

  • Electrolyte balance

  • Acid–base balance

• Balances maintained by the collective action of the urinary, respiratory, digestive, integumentary, endocrine, nervous, cardiovascular, and lymphatic systems.

Water Balance

• Newborn baby’s body weight is about 75% water.

• Young men average 55% to 60% water.

• Women average slightly less.

• Obese and elderly people as little as 45% by weight.

• Total body water (TBW) of a 70 kg (150 lb) young male is about 40 L.

Fluid Compartments

• Major fluid compartments of the body:

  • 65% intracellular fluid (ICF)

  • 35% extracellular fluid (ECF):

    • 25% tissue (interstitial) fluid

    • 8% blood plasma and lymphatic fluid

    • 2% transcellular fluid (cerebrospinal, synovial, peritoneal, pleural, and pericardial fluids; vitreous and aqueous humors of the eye; bile, and fluids of the digestive, urinary, and reproductive tracts)

Water Gain and Loss

• Fluid balance: When daily gains and losses are equal (about 2,500 mL/day).

• Gains come from two sources:

  • Preformed water (2,300 mL/day) ingested in food (700 mL/day) and drink (1,600 mL/day).

  • Metabolic water (200 mL/day) is a byproduct of aerobic metabolism and dehydration synthesis: C6H{12}O6 + 6 O2 \rightarrow 6 CO2 + 6 H2O

Water Gain and Loss (Continued)

• Obligatory water loss: Output that is relatively unavoidable, including expired air, cutaneous transpiration, sweat, fecal moisture, and minimum urine output (400 mL/day).

• Sensible water loss: Observable; 1,500-1,600 mL/day is in urine (roughly 60cc/hr), 200 mL/day is in feces, 100 mL/day is sweat in resting adult.

• Insensible water loss: Unnoticed; 300 mL/day in expired breath, 400 mL/day is cutaneous transpiration (diffuses through the epidermis and evaporates; does not come from sweat glands); loss varies greatly with environment and activity.

Regulation of Intake

• Thirst mainly governs fluid intake.

• Dehydration reduces blood volume and blood pressure and increases blood osmolarity.

• Osmoreceptors in the hypothalamus respond to angiotensin II (produced when BP drops) and to a rise in the osmolarity of ECF, communicating with other hypothalamic neurons and with the cerebral cortex.

Regulation of Intake (Continued)

• The hypothalamus produces antidiuretic hormone, which promotes water conservation.

• The cerebral cortex produces a conscious sense of thirst (intense with a 2% to 3% increase in plasma osmolarity or 10% to 15% blood loss).

• Salivation is inhibited with thirst due to sympathetic signals from the thirst center to salivary glands.

Regulation of Intake: Short-Term vs. Long-Term

• Short-term inhibition of thirst: cooling and moistening of the mouth, distension of the stomach and small intestine (satisfaction lasts 30 to 45 minutes, followed by water absorption into the bloodstream or thirst returns, designed to prevent overdrinking).

• Long-term inhibition of thirst: absorption of water from the small intestine reduces the osmolarity of blood, stopping the osmoreceptor response, promoting capillary filtration, and making saliva more abundant and watery (changes require 30 minutes or longer to take effect).

Regulation of Output

• The only way to control water output significantly is through variations in urine volume.

• The kidneys cannot replace water or electrolytes but can only slow the rate of water and electrolyte loss until water and electrolytes can be ingested.

• Control mechanisms of water output:

  • Changes in urine volume linked to adjustments in Na^+ reabsorption; as Na^+ is reabsorbed or excreted, water follows.

Regulation of Output: ADH

• Water output is slowed through the action of ADH.

• ADH secretion is triggered by hypothalamic osmoreceptors in response to dehydration.

• Aquaporins are synthesized in response to ADH, which are membrane proteins in renal collecting ducts that are channels allowing water to diffuse back into the renal medulla.

• Na^+ is still excreted, so the urine’s osmolarity (concentration) increases.

• The ADH system is an example of negative feedback; if osmolarity rises and/or blood volume falls, more ADH is secreted, slowing these trends; if osmolarity falls and/or blood volume rises, ADH release is inhibited, so the tubules reabsorb less water, urine output increases, and these trends are reversed.

Disorders of Water Balance

• The body is in a state of fluid imbalance if there is an abnormality of total volume, concentration, or distribution of fluid among the compartments.

• Fluid deficiency: fluid output exceeds intake over a long period of time.

  • Most serious effects: circulatory shock due to loss of blood volume, neurological dysfunction due to dehydration of brain cells, infant mortality from diarrhea.

  • Two types of deficiency: volume depletion and dehydration.

Disorders of Water Balance: Dehydration vs. Volume Depletion

• Dehydration (negative water balance): the body eliminates significantly more water than sodium, so ECF osmolarity rises, caused by lack of drinking water, diabetes, ADH hyposecretion (diabetes insipidus), profuse sweating, overuse of diuretics, affecting all fluid compartments (ICF, blood, and tissue fluid); infants are more vulnerable due to greater ratio of body surface to volume (more evaporation).

• Volume depletion (hypovolemia): occurs when proportionate amounts of water and sodium are lost without replacement, so total body water declines, but osmolarity remains normal, caused by hemorrhage, severe burns, chronic vomiting, diarrhea, or Addison disease.

Fluid Excess

• Fluid excess is less common than fluid deficiency because the kidneys are highly effective in compensating for excessive intake by excreting more urine; however, renal failure can lead to fluid retention.

Fluid Excess: Volume Excess vs. Hypotonic Hydration

• Two types of fluid excesses:

  • Volume excess: both Na^+ and water are retained, ECF remains isotonic, caused by aldosterone hypersecretion or renal failure.

  • Hypotonic hydration (water intoxication or positive water balance): more water than Na^+ is retained or ingested, ECF becomes hypotonic, which can cause cellular swelling; most severe effects are pulmonary and cerebral edema and death.

Electrolyte Balance

• Physiological functions of electrolytes: chemically reactive and participate in metabolism, determine electrical potential (charge difference) across cell membranes, strongly affect osmolarity of body fluids, and affect the body’s water content and distribution.

• Major cations (positive ions): Na^+, K^+, Ca^{2+}, Mg^{2+}, and H^+.

• Major anions (negative anions): Cl^−, HCO3^− (bicarbonate), and PO4^{3−}.

Electrolyte Balance (Continued)

• Great differences exist between electrolyte concentrations of blood plasma and intracellular fluid (ICF), but they have the same total osmolarity (300 mOsm/L), e.g., intracellular K is high and Na is low, and extracellular K is low and Na is high, but total osmolarity is roughly the same.

• Concentrations in tissue fluid (ECF) differ only slightly from those in the plasma.

Sodium

• Functions of Na^+: one of the principal ions responsible for the resting membrane potential, the inflow being an essential event in depolarizations that underlie nerve and muscle function; it is the principal cation in ECF, with sodium salts accounting for 90% to 95% of the osmolarity of ECF, and it is the most significant solute in determining total body water and distribution of water among fluid compartments.

Potassium

• Functions of K^+: produces (with sodium) the resting membrane potentials and action potentials of nerve and muscle cells; it is the most abundant cation of ICF, the greatest determinant of intracellular osmolarity and cell volume, and is essential for protein synthesis and other metabolic processes; the Na^+−K^+ pump is important for thermogenesis.

Potassium (Continued)

• Homeostasis: Potassium homeostasis is closely linked to that of sodium.

• 90% of K^+ in the glomerular filtrate is reabsorbed by the PCT, while the rest is excreted in urine.

• The DCT and cortical portion of the collecting duct secrete varying amounts of K^+ in response to blood levels.

• Aldosterone stimulates renal secretion of K^+.

Chloride

• Functions of Cl^−: the most abundant anion in ECF making a major contribution to ECF osmolarity, required for the formation of stomach acid (HCl), has a role in the chloride shift that accompanies CO_2 loading and unloading in RBCs, and plays a major role in regulating body pH.

Acids, Bases, and Buffers

• One of the most important aspects of homeostasis is that metabolism depends on enzymes that are sensitive to pH; slight deviations from the normal pH can shut down entire metabolic pathways and alter the structure and function of macromolecules such as proteins.

Acids, Bases, and