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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 processV. Specific renal process

VI. How does the kidney create hyperosmotic urine? VII. Renal regulation of sodium, water, and

potassiumVIII. Hydrogen ion regulationIX. 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. Bowman’s capsule- Bowman’s space

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B. Anatomy of the tubule:

i. Very narrow hollow tube of single celled epithelial tissue.

ii. Contiguous with

Bowman’s 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-πGC

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 Bowman’s 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