1. Kidney Anatomy and
Physiology
An Overview
Noah Hoffman
2006

2. Functions of the Kidney:
Maintaining balance
• Regulation of body fluid volume and
osmolality
• Regulation of electrolyte balance
• Regulation of acid-base balance
• Excretion of waste products (urea, ammonia,
drugs, toxins)
• Production and secretion of hormones
• Regulation of blood pressure

4. The Kidney and the Nephron
A. Renal Vein
B. Renal Artery
C. Ureter
D. Medulla
E. Renal Pelvis
F. Cortex
7. Ascending loop of
Henle
8. Descending loop of
Henle
9. Peritubular capillaries
10. Proximal tubule
11. Glomerulus
12. Distal tubule

5. The Nephron
• Functional unit of the kidney
(1,000,000)
• Responsible for urine formation:
– Filtration
– Secretion
– Reabsorption

6. Components of
the nephron
•Glomerulus
•Afferent and
Efferent arterioles
•Proximal Tubule
•Loop of Henle
•Distal Tubule
•Collecting Duct

7. Overview of nephron function
From http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEXCRET.html

8. Filtration

9. THE GLOMERULUS

10. Plasma is filtered through the
glomerular barrier
•Components of plasma cross the three layers of the
glomerular barrier during filtration
•Capillary endothelium
•Basement membrane (net negative charge)
•Epithelium of Bowman’s Capsule (Podocytes –filtration
slits allow size <60kD)
•The ability of a molecule to cross the membrane depends on
size, charge, and shape
• Glomerular filtrate therefore contains all molecules not
contained by the glomerular barrier - it is NOT URINE YET!

11. Glomerular Filtration Rate
(GFR)
• Measure of functional capacity of the
kidney
• Dependent on difference in pressures
between capillaries and Bowman’s
space
• Normal = 120 ml/min =7.2 L/h=180
L/day!! (99% of fluid filtered is reabs.)

12. Oncotic pressure
Oncotic pressure is the
component of total osmotic
pressure due to colloid
particles.
Water molecules cross the
membrane to equalize the
concentration of colloid
particles on each side.

13. Glomerular filtration rate (GFR)
• Depends on the difference in hydrostatic and oncotic
pressure on either side of the glomerular basement
membrane GFR
=
Glomerular Bowman’s
Capillary (GC) space (BS) Kf(PGC - PBS - COPGC)
P = hydrostatic
PGC PBS pressure
COPGC COPBS COP = colloid osmotic
pressure
Kf determined by
surface area and
permeability of H2O

14. Reabsorption
and secretion

15. Reabsorption
• Active Transport –requires ATP
– Na+, K+ ATP pumps
• Passive Transport-
– Na+ symporters (glucose, a.a., etc)
– Na+ antiporters (H+)
– Ion channels
– Osmosis

16. Factors influencing
Reabsorption
• Saturation: Transporters can get saturated
by high concentrations of a substance -
failure to resorb all of it results in its loss in
the urine (eg, renal threshold for glucose is
about 180mg/dl).
• Rate of flow of the filtrate: affects the time
available for the transporters to reabsorb
molecules.

17. What is Reabsorbed Where?
Proximal tubule - reabsorbs 65 % of filtered Na+ as well
as Cl-, Ca2+, PO4, HCO3-. 75-90% of H20. Glucose,
carbohydrates, amino acids, and small proteins are
also reabsorbed here.
Loop of Henle - reabsorbs 25% of filtered Na+.
Distal tubule - reabsorbs 8% of filtered Na+. Reabsorbs
HCO3-.
Collecting duct - reabsorbs the remaining 2% of Na+
only if the hormone aldosterone is present. H20
depending on hormone ADH.

19. Secretion
• Proximal tubule – uric acid, bile salts,
metabolites, some drugs, some
creatinine
• Distal tubule – Most active secretion
takes place here including organic
acids, K+, H+, drugs, Tamm-Horsfall
protein (main component of hyaline
casts).

20. Countercurrent exchange
• The structure and transport
properties of the loop of
Henle in the nephron create
the Countercurrent
multiplier effect.
• A substance to be exchanged
moves across a permeable
barrier in the direction from
greater to lesser
concentration.
Image from http://en.wikipedia.org/wiki/Countercurrent_exchange

21. Countercurrent exchange
• Countercurrnet exchange is
found throughout nature…
• Birds reduce heat loss
through their feet by heating
venous (returning) blood and
cooling arterial (outgoing)
blood in their legs.
Image from http://ecology.botany.ufl.edu/ecologyf02/homeostasis.html

22. Loop of Henle
– Goal= make isotonic filtrate
into hypertonic urine (don’t
waste H20!!)
– Counter-current multiplier:
• Descending loop is permeable
to Na+, Cl-, H20
• Ascending loop is impermeable
to H20- active NaCl transport
• Creates concentration gradient
in interstitium
• Urine actually leaves hypotonic
but CD takes adv in making
hypertonic

23. Hormones Produced by the
Kidney
• Renin:
– Released from juxtaglomerular apparatus when low blood
flow or low Na+. Renin leads to production of angiotensin II,
which in turn ultimately leads to retention of salt and water.
• Erythropoietin:
– Stimulates red blood cell development in bone marrow. Will
increase when blood oxygen low and anemia (low
hemoglobin).
• Vitamin D3:
– Enzyme converts Vit D to active form 1,25(OH)2VitD.
Involved in calcium homeostasis.

24. Renin, Angiotensin, Aldosterone:
Regulation of Salt/Water Balance

25. Renin/AII and Regulation of GFR
GFR = Kf(PGC - PBS - COPGC)
• “flight or fright”
∀⇑ sympathetic tone
• afferent arteriolar constriction (divert cardiac output to other
organs)
∀⇓PGC
∀⇓GFR and renal blood flow

26. Renin/AII and Regulation of GFR
GFR = Kf(PGC - PBS - COPGC)
•Low BP sensed in afferent
arteriole or low Na in distal tubule
•renin released
•renin converts angiotensinogen
to Angiotensin I
PGC⇑
•ACE converts AI to AII
•efferent > afferent arteriolar
constriction
∀⇑ PGC ⇒ ⇑ GFR (this is constricts
AUTOREGULATION of GFR)

27. Aldosterone
• Secreted by the adrenal glands in
response to angiotensin II or high
potassium
• Acts in distal nephron to increase
resorption of Na+ and Cl- and the
secretion of K+ and H+
• NaCl resorption causes passive
retention of H2O

28. Anti-Diuretic Hormone (ADH)
• Osmoreceptors in the brain (hypothalamus)
sense Na+ concentration of blood.
• High Na+ (blood is highly concentrated)
stimulates posterior pituitary to secrete ADH.
• ADH upregulates water channels on the
collecting ducts of the nephrons in the kidneys.
• This leads to increased water resorption and
decrease in Na concentration by dilution

29. Case I
• A 52 yo male is seen for a routine physical
exam for the first time in a few years. His
physician discovers that the patient has been
feeling more tired than usual for “a while.” He
also complains of increased thirst and
hunger, and says that he has to get up
several times at night to urinate.
• The lab measured a random blood glucose of
350 mg/dl, urine dipstick positive for glucose,
and urine albumin/creatinine of 40 mg/g.

30. Case 1 - DMII
• Diabetes mellitus type II (“adult onset”)
• Diabetes from Greek words meaning
"siphon" or "run through”; mellitus is Latin for
“sweet.”
• Saturation of glucose transporters results in
glucose in urine.
• Glucose in urine results in osmotic diuresis.
• Chronic hyperglycemia leads to
microvascular damage, including damage to
glomerular capillary wall, resulting in
microalbuminuria.

31. Case 2
• A 39-yr-old male with AIDS was admitted with
nausea, vomiting, abdominal pain, light-
headedness on standing, and weight loss.
During hospitalization, the patient developed
hypotonic polyuria with urine volumes of
9L/day associated with intense thirst.
• serum Na - 149 mmol/L [136-145]
• urine osmolality - 71 to 88 mmol/kg
[100-1000]

32. Case 2
• A water restriction test was performed, in which the
patient was given about 450 ml of 3% saline IV over
2 hours.
– serum osm - 306 mmol/kg [280-300]
– urine osm - 102
– urinary ADH - undetectable
• MR imaging showed changes in the posterior
pituitary.
• In response to treatment with desmopressin (10 g
twice daily by nasal spray), urine volumes decreased
to 2–3 liters per day. The patient later died of bowel
perforation. Autopsy showed evidence of damage to
the posterior pituitary caused by CMV infection.

33. Case 2 - Diabetes
Insipidus
• Inability to concentrate urine
despite high serum sodium and
osmolality. Results in large
volume of dilute urine.
• Central
– damage to the posterior pituitary
results in inadequate ADH
production
– treatment is exogenous ADH
• Nephrogenic
– kidney unresponsive to ADH
– can be hereditary or acquired
(eg, lithium therapy)
– serum ADH is high

34. Case 3
• A 61 year old male presented with confusion
and seizures two days after starting a new
medication (citalopram, an antidepressant).
– serum Na - 124 mmol/L [136–145]
– serum osmolarity - 263 mOsm/L [285–295]
– urine Na - 141 mEq/L [40-220]
– urine osmolarity - 400 mosm/L [100-1000]
– urine output - < 1L/day
• The patient's serum sodium gradually
normalized after the medication was
discontinued.

35. Case 3 - SIADH
• SIADH = syndrome of inappropriate
antidiuretic hormone secretion
• Open channels in the collecting duct lead to
excessive water resorption and a dilutional
hyponatremia.
• can be caused by brain injury, ectopic
production by tumors, various drugs, major
surgery, pulmonary diseases, exogenous
ADH
• Treatment includes water restriction and salt
administration