6-1 The Urinary System

The Terrestrial Environment

• Lots of O2
• Not so much H2O
• We live in an osmotically hostile environment
• Must maintain water balance – more after the exam

The Kidney

• Filtration and excretion
• Metabolic wastes and toxins
• Hormone production
• Homeostasis of body fluids

The Kidney

• Filtration and excretion
• Hormone production
• Calcitriol
• Works with PTH to increase plasma [Ca+]
• Erythropoietin
• ↑RBC production
• Renin
• Not a hormone but important for hormonal control
• Homeostasis of body fluids

The Kidney

• Filtration and excretion
• Hormone production
• Homeostasis of body fluids
• Regulate
• Blood volume
• Blood pressure
• Electrolyte concentration
• Blood pH
• Detoxification
• Deamination of nitrogenous wastes
• Clear hormones and drugs

Nitrogenous Wastes

• Urea
• proteins→amino acids →NH2 removed →forms ammonia, liver converts to urea
• Uric acid
• nucleic acid catabolism
• Creatinine
• creatine phosphate catabolism
• Renal failure
• azotemia: ↑BUN, nitrogenous wastes in blood, Creatinine
• uremia: toxic effects as wastes accumulate

Gout

Gout

6-2 Urinary Anatomy

The Kidney

• Paired, kidney-bean shaped organ
• 4-5” long, 2-3” wide, ~1” thick
• 140-150 grams (0.4% body mass)
• Found on the posterior abdominal wall deep to ribs 11 and 12, superficial to parietal peritoneum (retroperitoneal)
• Receives 20-25% of resting cardiac output

Anatomy of the Urinary System �

The Kidney

Anatomy of a Kidney�

Circulation of Blood�

Anatomy of a Renal Lobe�

The Nephron

• Functional unit of the kidney
• 1 million nephrons in the cortex of each kidney
• 85% Cortical nephrons
• 15% Juxtamedullary nephrons

The Nephron

• Functional unit of the kidney
• 1 million nephrons in the cortex of each kidney
• 85% Cortical nephrons
• 15% Juxtamedullary nephrons
• Renal corpuscle
• Filtration

The Nephron

• Functional unit of the kidney
• 1 million nephrons in the cortex of each kidney
• 85% Cortical nephrons
• 15% Juxtamedullary nephrons
• Renal corpuscle
• Renal tubule
• Secretion and reabsorption
• Filtrate drains into collecting structures, becoming urine

Anatomy of a Nephron�

Two Types of Nephrons:Cortical and Juxtamedullary

Urine

• Appearance
• Colorless to deep amber
• Color due to urochrome
• Influenced by diet and health
• Odor
• Distinctive smell, changes indicative of diet, disease, hydration
• Breakdown of asparagusic acid causes ‘asparagus pee’ but only some can smell it
• Specific gravity – density of urine/density of water
• 1.001-1.028
• Osmolarity
• 50-1200 mOsm/L

Formation and Flow of Urine�

6-3 Urine Formation: Filtration

Urine Formation

• Urine is formed by 3 distinct processes:
• 1. Filtration = Occurs in the renal corpuscle; forms filtrate (not urine yet)
• Water, ions, small proteins, amino acids, hormones, etc.
• 2. Reabsorption
• 3. Secretion

Urine Formation

• Urine is formed by 3 distinct processes:
• 1. Filtration
• 2. Reabsorption = Most occurs in the proximal nephron; reclaiming all the good stuff
• Glucose, lipids, amino acids, etc.
• 3. Secretion

Urine Formation

• Urine is formed by 3 distinct processes:
• 1. Filtration
• 2. Reabsorption
• 3. Secretion = ”Unwanted” substances are added to the filtrate; occurs throughout the nephron
• H+, urea, creatinine, uric acid

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Anatomy of a Renal Corpuscle�

The Nephron – The Renal Corpuscle

• The glomerulus 🡪 tuft of capillaries
• With podocytes forms the filtration membrane
• Afferent and efferent arterioles
• Bowman’s capsule encapsulates the capsular space
• Parietal layer
• Visceral layer
• Juxtaglomerular apparatus:
• Macula densa cells of the DCT
• Extraglomerular cells of the afferent arteriole
• Mesangial cells in the vascular pole.
• JGA is critical for autoregulation of glomerular filtration rate

JGA

Glomerular filtration

• Driven by hydrostatic pressure inside the glomerular capillaries
• Approximately 20% of plasma becomes filtrate
• 180 liters/day (48 gallons) filtered; 0.5-2 liters excreted as urine
• You’d “bleed out” from your kidneys in less than an hour if 99% of it wasn’t reabsorbed!
• Filtering capacity is regulated and can be enhanced by
• Thinness and surface area of filtration membrane (JGA)
• Glomerular capillary blood pressure

Glomerular Filtration

Cells and platelets

Large proteins

Medium proteins,

but allows small

inorganic and

organic molecules

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Filtration membrane

Glomerular filtration

• BHP drives filtrate out
• COP and CP oppose filtration

Glomerular filtration

• Glomerular filtration rate (GFR) = volume of filtrate produced by both kidneys per minute
• 125 mL/min X 60 min X 24 hr = 180 L/day
• Control of GFR:
• 1. Autroregulation – GFR remains constant
• 2. Hormonal regulation – Epinephine and norepinephrine, renin-angiotensin-aldosterone system (RAAS), and natriuretic peptides
• 3. Autonomic regulation – Mostly sympathetic autonomic regulation and associated with acute crises (hemorrage, dehydration, anaphylaxis, etc.)

Autoregulation of GFR

Autoregulation is accomplished primarily with the afferent arteriole using two mechanisms:

1. Myogenic response

• ↑BP stretches afferent arteriole smooth muscles cells which contract and ↓diameter of the lumen, returning GFR to a normal range
• ↓ BP relaxes the afferent arteriole 🡪 ↑ blood flow and ↑ GFR.

2. Tubuloglomerular feedback

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Autoregulation of GFR

Autoregulation is accomplished primarily with the afferent arteriole using two mechanisms:

1. Myogenic response
2. Tubuloglomerular feedback
• Macula densa cells of the JGA monitor filtrate in the DCT
• ↑filtrate [Osm] indicate a high GFR and ↓[Osm] indicate a ↓GFR
• Macula densa cells cause the constriction and dilation of the afferent arteriole to modulate GFR

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Hormonal regulation of GFR

• Atrial and Brain Natriuretic Peptides
• Increased BP/volume 🡪 stretches atrial myocytes 🡪 ANP release
• Vasodilates afferent and constricts efferent arterioles 🡪 ↑ GFR
• Relaxes mesangial cells 🡪 ↑ glomerular surface area 🡪 ↑ GFR
• ↑ cortical and medullary blood flow, washing out the medulla and diluting urine (diuresis)
• Inhibits renin secretion 🡪 ↓ angiotensin II, aldosterone, and anti-diuretic hormone (ADH)
• Reduces Na⁺ reabsorption in the DCT and CD

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Hormonal regulation of GFR

• Renin - Not a hormone, but released by the JGA when:
• Glomerular blood pressure is reduced
• Macula densa cells detect low [Na⁺] and [Cl^-] in the DCT
• It is stimulated by the sympathetic autonomic nervous system
• Results in the activation of the renin-angiotensin-aldosterone system (RAAS)
• Angiotensin II
• Constricts afferent and efferent arterioles = ↓GFR
• Releases ADH and aldosterone
• Increases thirst and salt cravings
• Increases Na⁺ reabsorption in PCT
• Increases thirst
• Epinephrine and Norepinephrine
• Releases renin & constricts afferent arteriole ↓GFR

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Autonomic regulation of GFR

• No parasympathetic innervation
• Sympathetic fibers innervate
• JGA 🡪 Promotes renin secretion
• Afferent and efferent arterioles 🡪 ↓GFR
• Nephron tubule 🡪 ↑Na⁺ and water reabsorption
• Epinephrine and norepinephrine are released by sympathetic NS

6-4 Urine Formation: Secretion and Reabsorption

Tubular reabsorption and secretion

• Nephron must reabsorb 99% of 50 gal filtrate
• Two routes for tubular reabsorption
• Transcellular and paracellular

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• Proximal Convoluted Tubule
• 65% of filtrate reabsorbed in PCT
• Reabsorbs water and solutes in proportion
• High metabolic rate
• About 6% of your resting metabolism is due to the PCT
• High surface area due to microvilli

PCT transport mechanisms

• Lumenal [Na+] = 145 mmol
• Intracellular [Na+] = 10 mmol
• Interstitial [Na+] = 145 mmol
• Na+ gradient allows symport and antiport transport of molecules into and out of tubular fluid
• Na+ H+ antiporter;
• Na+ HCO3- symporter
• Na+ glucose symporter

Sodium and chloride reabsorption

• PCT – 67% reabsorbed
• Used for cotransport of other molecules
• tDL – 0%
• None
• tAL/TAL – 25% reabsorbed
• tAL paracellular
• TAL via symporter that leaves + charge in tubule lumen
• DCT – 5% reabsorbed
• 5% reabsorbed (more with aldosterone)
• CD – 3% reabsorbed
• Through leak channels targeted by aldosterone

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Water reabsorption

• PCT – 67% reabsorption
• Via aquaporins and leaky tight junctions
• tDL – 15%
• Permeable to water, not to ions
• Travels through a gradient
• tAL – None
• TAL – None
• DCT – 10-15%
• ADH inserts some aquaporins
• CD – 5-10%
• Concentration gradient of medulla and # of aquaporins (ADH) determines net water reabsorption in the CD.

Urine formation

• tDL is permeable to water, not to ions
• tAL and TAL are permeable to ions, not to H2O
• 1 Na+ 1 K+ 2Cl- cotransporter of TAL moves NaCl out of filtrate (K+ is cycled)
• Symporters can only generate a 200 mOsm difference
• As filtrate moves down the tDL osmosis drives water into the medulla
• ADH modulates permeability of CD

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Urine formation

Medullary [osm]

50 mOsm

1200 mOsm

Urine formation

• Countercurrent multiplication allows the JM nephron loop to generate gradient
• Countercurrent exchange in the vasa recta protects the gradient
• Urea diffusing from filtrate into the medulla at the CD accounts for 40% of the osmolarity of deep medulla

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Kangaroo rat

• Desert dwelling rodent of the SW US
• All water needs are met with metabolic water
• 100 g Fats 🡪 110 ml H2O
• 100 g Protein 🡪 40 ml H2O but it takes about 40 ml of H2O to excrete the urea generated
• 100 g Carbs 🡪 55 ml H2O
• Deeper medulla and longer LoH allows for a greater concentrating ability
• 6,000 mOsm!

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Nitrogenous waste

• Protein catabolism generates ammonia which the liver converts to urea
• Nucleic acid catabolism generates uric acid
• Creatinine phosphate catabolism (anaerobic muscle activity) generates creatinine
• PCT – 67% reabsorbed
• LoH – Only urea in tAL
• DCT – None
• CD – Variable with urine flow
• Urea is recycled between the tDL and CD to maintain high medullary osmotic concentration and countercurrent exchange of vasa recta

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Glucose

• Normal plasma [glucose] is 70-100 mg/dL
• 100% of glucose is reabsorbed into PCT cells via Na-Glucose transporter and diffuses into the interstitium via facilitated diffusion
• Plasma [glucose] over 250 mg/dL cannot all be reabsorbed
• A symptom of diabetes mellitus is elevated plasma [glucose]

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Other components of filtrate

• Calcium
• Mostly reabsorbed in PCT
• TAL and DCT reabsorb more Ca++ in response to Vitamin D and Parathyroid Hormone; high plasma [Ca++] inhibits Ca++ reabsorption
• Potassium
• Mostly reabsorbed in PCT
• Is exchanged for Na+ in DCT under influence of aldosterone
• Amino acids
• 100% of amino acids are reabsorbed in the PCT via Na+ cotransport
• Whole proteins
• 100% are reabsorbed via endocytosis in the PCT
• Ammonia
• PCT and DCT secrete variable amount via Na+ cotransport
• H+ and HCO3+
• Renal H+ excretion and HCO3- reabsorption/creation are essential
• HCO3- is reabsorbed in the PCT and LoH while H+ is mostly secreted in PCT

Tubular reabsorption review

• 5 components of the nephron tubule:
• 1. Proximal convoluted tubule
• 67% of filtrate
• 2. Thin descending loop
• H2O
• 3. Thin ascending loop
• NaCl, no H2O 
• 4. Thick ascending loop
• NaCl, no H2O
• 5. Distal convoluted tubule
• NaCl, K+, H+, Ca++, etc.
• 6. Collecting Duct
•   Variable H2O

Tubular Hormonal regulation

• Antidiuretic hormone (ADH/AVP)
• Secreted by the pituitary gland in response to angiotensin II or ↑[osm]
• Increases concentration of urine by causing aquaporins to insert in wall of CD
• Inhibited by EtOH

Tubular Hormonal regulation

• Aldosterone
• Secreted from adrenal cortex in response to ↓Na⁺, ↑K⁺, or RAAS
• Promotes Na⁺ and water retention, and K⁺ elimination in principal cells of DCT and CD
• Promotes H⁺ loss in intercalated cells of DCT and CD
• Reabsorbing more ions 🡪 ↑H₂O
• Increases thirst
• Parathyroid hormone
• Secreted from parathryoid glands in response to ↓[Ca++]
• Promotes Mg++ and Ca++ reabsorption
• Promotes Calcitriol synthesis by kidneys

6-5 Urination and Pathologies

Anatomy of Urinary Bladder

• Hollow, distensible muscular organ with capacity of 700 - 800 mL in females (1200 ml in males)
• Trigone is smooth flat area bordered by 2 ureteral openings and one urethral opening

Male and Female Urethras

Micturation

Urinary Incontinence

• Lack of voluntary control over micturition
• normal in 2 or 3 year olds because neurons to sphincter muscle not developed
• Stress incontinence in adults
• caused by increases in abdominal pressure that result in leaking of urine from the bladder
• coughing, sneezing, laughing, exercising, walking
• injury to the nerves, loss of bladder flexibility, or damage to the sphincter

Diuretics

• Substances that slow renal reabsorption of water & cause diuresis (increased urine flow rate)
• caffeine which inhibits Na+ reabsorption
• alcohol which inhibits secretion of ADH
• prescription medicines can act on the PCT, loop of Henle or DCT
• Used for treatment of Congestive Heart failure and hypertension

Diabetes

• Chronic polyuria of metabolic origin
• With hyperglycemia and glycosuria
• diabetes mellitus I and II, insulin hyposecretion/insensitivity
• gestational diabetes, 1 to 3% of pregnancies
• With glycosuria but no hyperglycemia
• renal diabetes, hereditary deficiency of glucose transporters
• With no hyperglycemia or glycosuria
• diabetes insipidus, ADH hyposecretion

Dialysis Therapy

• Kidney function is so impaired the blood must be cleansed artificially
• separation of large solutes from smaller ones by a selectively permeable membrane
• Artificial kidney machine performs hemodialysis
• directly filters blood because blood flows through tubing surrounded by dialysis solution
• cleansed blood flows back into the body

Waste Management in Other Body Systems

• Buffers bind excess H+
• Blood transports wastes
• Liver is site for metabolic recycling
• conversion of amino acids into glucose, glucose into fatty acids or toxic into less toxic substances
• Lungs excrete CO2 and heat
• Sweat glands eliminate heat, water, salt & urea
• GI tract eliminates solid wastes, CO2, water, salt and heat