1

Functions of the kidney

1. Regulation of inorganic ions (Na+, K+, Ca++, Cl-, Pi, Mg++)

2. Regulation of water balance & osmolality

3. Excretion of nitrogenous wastes (urea, creatinine)

4. Excretion of foreign chemicals (drugs, pollutants, etc.)

5. Regulation of pH, and HCO3-

6. Synthesis of renin

7. Synthesis of erythropoietin; activation of vitamin D3

8. Gluconeogenesis (liver much more important)

2

Structure of urinary system

fig 14-1

3

Structure of kidney

fig 14-4

4

Structure of nephron & blood supply

fig 14-2

Nephron:Bowman’s capsule (C)proximal tubule (C)loop of Henle (M)distal tubule (C)collecting duct (C, M)

Blood supplyafferent arteriole (C)glomerular capillaries (C)efferent arteriole (C)peritubular capillaries (C)vasa recta (M)venule (C)

(C) = cortex(M) = medulla

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Blood flow: afferent arteriole glomerular capillaries efferent arteriole

Filtration: from glomerular capillaries into Bowman’s capsule

Cell types: juxtaglomerular apparatus (macula densa + juxtaglomerular cells)podocytes

Structure of glomerulus (renal corpuscle)

fig 14-3

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From plasma through capillary endothelial cell fenestrae & podocyte filtration slits into Bowman’s capsule.

Fluid in Bowman’s capsule is protein-free filtrate of plasma

Direction of filtration

fig 14-3b

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Macula densa: specialized cells in wall of distal tubule

Juxtaglomerular cells: contain renin, sympathetic nerves

Juxtaglomerular apparatus

fig 14-5

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Filtration: glomerular capillaries Bowman’s capsule

Secretion: peritubular capillaries tubular fluid

Reabsorption: tubular fluid peritubular capillaries

Excretion = filtration + secretion – reabsorption

Filtration, reabsorption, secretion, excretion

fig 14-6

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Substance X: filtered & entirely secreted (rare)

Substance Y: filtered & partially reabsorbed (Na+, K+, water)

Substance Z: filtered & entirely reabsorbed (glucose, amino acids)

Kidney handling of various substances

fig 14-7

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Glomerular filtration barrier

fig 14-3c

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Forces of filtration

fig 14-8

Compare with Starling forces in muscle capillaries

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Important numbers

fig 14-8

Resting cardiac output: ~5L/min

Renal blood flow: ~1.2 L/min (i.e. about 25% of CO)

Renal plasma flow: ~650 ml/min (~55% of blood is plasma)

Glomerular filtration rate: ~120 ml/min (i.e. about 20% of renal plasma flow)

Therefore, of plasma flowing through glomerular capillaries, ~20% is filtered into Bowman’s capsule and only 80% enters the efferent arteriole

GFR of 120 ml/min = ~180 L/day (i.e. plasma is filtered 60x each day)

Urine flow rate = ~1 ml/min (i.e. 99+% water reabsorbed)

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Reabsorption

fig 14-10

reabsorption

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Reabsorption of glucose & amino acids

Glucose & amino acids are freely filtered

At normal plasma concentrations they are all entirely reabsorbed

Hence, urine [glucose] & [amino acid] are zero (see substance Z fig 14-7)

Mechanism: Na+ linked co-transport at the luminal membrane of the proximal tubule

In an untreated diabetic, plasma [glucose] is high, therefore the amount of glucose filtered is greater then the maximum transport rate of the transporters; hence glucose appears in the urine.

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Reabsorption of urea

Urea is freely filtered

As water is reabsorbed, the tubular [urea] rises

Urea is passively reabsorbed down its concentration gradient (see substance Y fig 14-7)

About half the filtered urea is excreted

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Measurement of glomerular filtration rate

Inulin (~5000 M.Wt. polysaccharide) prepared from plants

Inulin is filtered, not reabsorbed, not secreted

Therefore all the inulin that is filtered is excreted

Inulin filtered = GFR x [inulin]plasma

Inulin excreted = urine flow rate x [inulin]urine

Therefore GFR = urine flow rate x [inulin]urine

[inulin]plasma

Clinically, creatinine is used to measure GFR

Creatinine is released at a constant rate from muscle

Creatinine properties are similar, but not identical, to inulin

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Measurement of glomerular filtration rate

fig 14-11

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Sodium balance

Most NaCl intake added during food preparation

Sweat output depends on body temperature

Urine output of NaCl is regulated by blood pressure

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Water balance

Metabolically produced by oxidation of H-containing nutrients

Insensible loss: expiration of 37 saturated air, evaporation through skin (different from sweat)

Urine output regulated by vasopressin (antidiuretic hormone ADH)

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Total body NaCl and extracellular volume

total body NaCl

extracellular osmolality

vasopressin release

water retention by kidneys

extracellular volume

Because vasopressin release is sensitive to changes in osmolality, any change in total body NaCl will result in a proportional change in extracellular volume

21

Sodium handling by the kidney

Of the sodium filtered ~99.5% is reabsorbed, 0.5% excreted

Sympathetic nervous system regulates glomerular filtration rate

Sodium reabsorption:

~70% from proximal tubule (unregulated)

~20% from ascending limb of loop of Henle (unregulated)

~5% from distal tubule (unregulated)

3-5% from collecting duct (regulated by aldosterone & atrial natriuretic peptide-less

important)

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Regulation of sodium excretion

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Sympathetic nervous system on sodium excretion

1. action on glomerular filtration rate

blood pressure discharge from carotid sinus SNS activity glomerular filtration rate Na+ filtered Na+ excreted

2. action on renin release

blood pressure afferent arteriole pressure renin angiotensin I,II aldosterone Na+ reabsorbed Na+ excreted

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Renin angiotensin aldosterone system

fig 14-19

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Renin angiotensin aldosterone system on Na+ excretion

fig 14-20

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Renin angiotensin aldosterone system on Na+ excretion

Renin release stimulated by:

1. sympathetic nervous activity

2. blood pressure in afferent arteriole

3. Na+ and Cl- in tubular fluid at macula densa

Angiotensin II actions:

1. general vasoconstriction

2. stimulates aldosterone release from adrenal cortex

Aldosterone release stimulated by:

1. plasma angiotensin II levels

2. plasma potassium concentration

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Actions of aldosterone

fig 14-13

Aldosterone actions:

Na+ channel activity, K+ channel activity, Na+/K+ ATPase pump

Note: large Na+, K+ shows high concentration & vice versa

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Atrial natriuretic peptide on Na+ excretion

fig 14-21

ANP actions:

1. Na+ reabsorption from deep medullary collecting duct

2. glomerular filtration rate

Both actions Na+ excretion

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Water transport & vasopressin (ADH) dependence

Transport mechanism:

passive diffusion through aquaporin channels down osmotic gradient

Reabsorption:

~99% of filtered water is reabsorbed

Sites of reabsorption:

~70% from proximal tubule

~15% from descending limb of loop of Henle

0% from Henle’s ascending limb & distal tubule

0-15% from collecting duct depending on plasma vasopressin level

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Vasopressin (ADH) release & actions

Vasopressin release stimulated by:

1. slight (1%) increase in plasma osmolality

2. large (~15%) reduction in plasma volume

Vasopressin action:

increases permeability of collecting duct to water

Renal medulla

has osmotic gradient from 300 mOsm/kg at cortical border to 1200 mOsm/kg at deepest part of medulla (mechanism not necessary)

ADH levels collecting duct permeability water reabsorption urine volume with osmolality

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Vasopressin action

fig 14-15

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Water transport & vasopressin actions

fig 14-23 fig 14-22

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Sweating without water replacement

fig 14-24

Sweat is hypotonic (i.e. osmolality < plasma)

Gatorade story

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Regulation of thirst

Sensation of thirst stimulated by:1. 1% osmolality2. >15% blood volume3. angiotensin II4. dry mouth, throat

Sensation of thirst inhibited by:1. GI metering of water intake

fig 14-25

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Potassium excretion

Reabsorption from:

proximal tubule

Henle’s ascending limb

(collecting duct)

Secretion into:

collecting duct (regulated process)

fig 14-26

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Regulation of potassium excretion

fig 14-27