Functions of the kidney

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
Nephron Bowmans capsule (C) proximal tubule
(C) loop of Henle (M) distal tubule
(C) collecting duct (C, M) Blood
supply afferent arteriole (C) glomerular
capillaries (C) efferent arteriole
(C) peritubular capillaries (C) vasa recta
(M) venule (C) (C) cortex (M) medulla
fig 14-2
5
Structure of glomerulus (renal corpuscle)
Blood flow afferent arteriole ? glomerular
capillaries ? efferent arteriole Filtration from
glomerular capillaries into Bowmans capsule Cell
types juxtaglomerular apparatus (macula densa
juxtaglomerular cells) podocytes
fig 14-3
6
Direction of filtration
From plasma through capillary endothelial cell
fenestrae podocyte filtration slits into
Bowmans capsule. Fluid in Bowmans capsule is
protein-free filtrate of plasma
fig 14-3b
7
Juxtaglomerular apparatus
Macula densa specialized cells in wall of distal
tubule Juxtaglomerular cells contain renin,
sympathetic nerves
fig 14-5
8
Filtration, reabsorption, secretion, excretion
Filtration glomerular capillaries ? Bowmans
capsule Secretion peritubular capillaries ?
tubular fluid Reabsorption tubular fluid ?
peritubular capillaries Excretion filtration
secretion reabsorption
fig 14-6
9
Kidney handling of various substances
Substance X filtered entirely secreted
(rare) Substance Y filtered partially
reabsorbed (Na, K, water) Substance Z
filtered entirely reabsorbed (glucose, amino
acids)
fig 14-7
10
Glomerular filtration barrier
fig 14-3c
11
Forces of filtration
Compare with Starling forces in muscle capillaries
fig 14-8
12
Important numbers
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 Bowmans 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)
fig 14-8
13
Reabsorption
reabsorption
fig 14-10
14
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.
15
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
16
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
inulinplasma Inulin excreted urine flow rate
x inulinurine Therefore GFR urine flow rate
x inulinurine inulinplasma 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
17
Measurement of glomerular filtration rate
fig 14-11
18
Sodium balance
Most NaCl intake added during food
preparation Sweat output depends on body
temperature Urine output of NaCl is regulated by
blood pressure
19
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)
20
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)
22
Regulation of sodium excretion
23
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
• action on renin release
• ? blood pressure ?? afferent arteriole pressure
  ?? renin ?
• ?? angiotensin I,II ?? aldosterone ?? Na
  reabsorbed ?
• ?? Na excreted

24
Renin angiotensin aldosterone system
fig 14-19
25
Renin angiotensin aldosterone system on Na
excretion
fig 14-20
26
Renin angiotensin aldosterone system on Na
excretion

• Renin release stimulated by
• 1. ? sympathetic nervous activity
• 2. ? blood pressure in afferent arteriole
• ? Na and Cl- in tubular fluid at macula densa
• Angiotensin II actions
• general vasoconstriction
• stimulates aldosterone release from adrenal
  cortex
• Aldosterone release stimulated by
• 1. ? plasma angiotensin II levels
• 2. ? plasma potassium concentration

27
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
28
Atrial natriuretic peptide on Na excretion

• ANP actions
• ? Na reabsorption from deep medullary collecting
  duct
• 2. ? glomerular filtration rate
• Both actions ?? Na excretion

fig 14-21
29
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 Henles ascending limb
distal tubule 0-15 from collecting duct
depending on plasma vasopressin level
30
Vasopressin (ADH) release actions

• Vasopressin release stimulated by
• slight (1) increase in plasma osmolality
• 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

31
Vasopressin action
fig 14-15
32
Water transport vasopressin actions
fig 14-23
fig 14-22
33
Sweating without water replacement
fig 14-24
Sweat is hypotonic (i.e. osmolality lt
plasma) Gatorade story
34
Regulation of thirst

• Sensation of thirst stimulated by
• 1 ? osmolality
• 2. gt15 ? blood volume
• ? angiotensin II
• 4. dry mouth, throat
• Sensation of thirst inhibited by
• 1. GI metering of water intake

fig 14-25
35
Potassium excretion
Reabsorption from proximal tubule Henles
ascending limb (collecting duct) Secretion
into collecting duct (regulated process)
fig 14-26
36
Regulation of potassium excretion
fig 14-27