Brief overview of mammalian renal physiology

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Brief overview of mammalian renal physiology

• Jason Williams
• University of Nevada Las Vegas
• 2-28-07

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Outline for renal physiology lecture

• I. Specific functions of the kidney
• II. Kidney structure
• III. Nephron the functional unit of the kidney
• IV. Basic renal process
• V. Specific renal process
• VI. How does the kidney create hyperosmotic
  urine?
• VII. Renal regulation of sodium, water, and
  potassium
• VIII. Hydrogen ion regulation
• IX. Diuretics and kidney disease

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• What does the kidney do?
• Kidneys filter plasma to regulate the makeup of
  the interstitial fluid and blood.

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What is interstitial fluid?
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Where is Interstitial fluid located?
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• I. Specific Functions of the Kidney
• 1. Form urine (95 water, 5 solutes)
• A. Removal of metabolic waste from plasma
• i. urea (protein breakdown)
• ii. uric acid (nucleic acid breakdown)
• - insoluble in blood
• - can precipitate out in blood and cause gout
• iii. creatinine (muscular creatine phosphate
  breakdown)

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• B. Removal of foreign compounds
• - drugs, food additives, pesticides

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• C. maintain water, inorganic ion concentrations
• i. important for proper fluid volume

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2. Other Functions of the kidney

• A. Acts as endocrine gland
• i. erythropoietin
• ii. Renin
• iii. 1,25 dihydroxyvitamin D3
• B. Gluconeogenesis during times of fasting
• i. amino acids ? glucose

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• II. Structure of the Kidney
• 1. Location
• - retroperitoneal
• - superior lumbar region
• - twelfth thoracic to the third
• lumbar vertebrae

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• 2. Part of the urinary system
• - ureters
• - bladder
• - urethra

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3. External anatomy of the kidney

• - Bean shaped
• - vertical cleft called the renal hilus
• - Ureters, renal blood vessels, lymphatics,
• and nerves enter and exit at the hilus

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• 4. Internal anatomy of a kidney
• The kidney has three main regions
• A. Renal Cortex
• - outer region (granular)
• B. Renal Medulla
• - inner region (striated)
• - consists of a number of
• triangular structures called
• renal pyramids
• C. Renal pelvis
• - major calyces

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• III. Nephron The functional unit of the kidney
• i. smallest unit capable of forming urine
• ii. microscopic, each kidney has about 1 million

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• 1. The nephron consists of two distinct regions
• A. Renal corpuscle
• B. Tubule

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A. Anatomy of the renal corpuscle

• i. Glomerulus
• - Afferent and efferent arterioles
• ii. Bowmans capsule
• - Bowmans space

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B. Anatomy of the tubule

• i. Very narrow hollow tube of single celled
  epithelial tissue.
• ii. Contiguous with
• Bowmans capsule

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C. Tubule consists of

• 1. Proximal tubule (convoluted and straight)
• 2. Loop of Henle (descending and ascending)
• 3. Distal convoluted tubule
• 4. Connecting tubule
• 5. Collecting duct

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D. Vascularization of the nephron

• Two sets of capillaries
• a. Glomerulus
• b. Peritubular capillaries
• Connected by efferent
• arteriole

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IV. Basic renal process

• 1. Urine formation
• A. begins with glomerular filtration ends with
  urine formation.

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• B. glomerular filtrate has essentially the same
  concentrations of solutes as blood plasma, minus
  proteins

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B. Glomerular filtrate ? Urine
Substance Amount Filtered per day Amount excreted per day
Water, L 180 1.8
Sodium, g 630 3.2
Glucose, g 180 0
Urea, g 54 30
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C. How is glomerular filtrate altered as it moves
through the tubule?

• -Tubular reabsorption
• -Tubular secretion
• Excreted filtered - reabsorbed secreted

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B. Glomerular filtrate ? Urine
Substance Amount Filtered per day Amount excreted per day
Water, L 180 1.8
Urea, g 54 30
Penicillin 3 10
Creatinine, g 20 20
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V. Closer look at renal processes

• 1. glomerular filtration
• - glomerular filtrate has essentially the same
  concentrations of solutes as blood plasma,
  minus proteins

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A. Glomerular filtrate passes through three layers

• i. Single-celled capillary endothelium
• ?
• ii. Non-cellular proteinaceous
• layer of basement membrane.
• ?
• iii. Single-celled epithelium
• lining (podocytes)

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B. Forces involved in filtration

• Net glomerular filtration
• pressure
• PGC-PBS-pGC
• 55 - 15 - 30 10mmHG

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C. Glomerular Filtration Rate (GFR)

• GFR the volume of fluid/plasma filtered from
  the glomeruli to the Bowmans space per unit
  time.
• GFR 180 L/day for average adult
• blood volume filtered 60 times per
  day
• GFR is under physiological regulation

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2. Clinical determination of GFR
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• A. Introduction
• i. Estimated glomerular filtration rate by
  measuring inulin and creatinine clearance.
• ii. Why? Abnormal GFR may suggest renal disease
  (the leading cause of death in captive cheetahs)

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• B. Brief Materials and Methods
• i. measure of GFR
• 1. injected cats with known amount of inulin
• Inulin
• - foreign polysaccharide
• - fully filtered
• - not reabsorbed

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B. Brief Materials and Methods (Cont.)

• 2. Determine amount of inulin in serum and urine
  sample
• 3. Calculate GFR in milliliters
• (Urine conc. of inulin) X (urine volume)
  (serum conc. of inulin)
• 4. Report final GFR as ml min-1 kg-1

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C. Results
Ccr creatinine clearance rate - Creatinine
produced endogenously - typically only
filtered - measured in same fashion as inulin
GFR
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D. Conclusions
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Tubular Reabsorption
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3. Reabsorption

• A. Occurs in proximal tubule and loop of Henle

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• B. General process
• i. Luminal membrane ? basolateral membrane ?
  interstitial fluid ? peritubular capillary

ii. Tight junction ? interstitial fluid ?
peritubular capillary
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• C. Tubular reabsorption occurs by
• i. Diffusion
• water, urea, other lipid soluble substances
• ii. Mediated transport
• Move substances uphill against diffusion
  gradient. (glucose, amino acids, etc.)

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D. Efficiency of tubular reabsorption
Substance Amount Filtered per day Amount excreted per day Percent reabsorbed
Water, L 180 1.8 99.0
Sodium, g 630 3.2 99.5
Glucose, g 180 0 100
Urea, g 54 30 44
Rates of reabsorption are under physiological
control
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Tubular Secretion
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4. Tubular Secretion

• A. Moves substances from
• - peritubular capillary ? tubular lumen
• B. occurs by diffusion or mediated transport
• C. secreted substances
• hydrogen ions, potassium, foreign chemicals,
  choline etc.

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5. Division of Labor in Nephron

• A. Renal corpuscle filtrate
• B. Proximal tubule primary reabsorption
• C. Proximal tubule primary secretion

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• D. Renal D. Loop of Henle reabsorption
• E. Distal segments fine tuning, under
  homeostatic control