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Processes involve
active transport
passive transport, or
osmotic gradients
Marc Imhotep Cray, M.D. 7
Overview (4)
Most of water and solutes (eg, sodium, glucose, bicarbonate,
amino acids) are reabsorbed during passage through proximal
convoluted tubule (PCT)
Further concentration occurs in countercurrent system of loop of Henle
Seeley R. et.al. Seeley’s Anatomy & Physiology 10th ed. Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated
New York, NY: McGraw-Hill , 2010. Pharmacology, Updated Edition. Saunders, 2014
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
13
Functional Anatomy
Kidneys contribute to several important processes, including
regulation of fluid volume
regulation of electrolyte and acid-base balance
excretion of metabolic wastes and
elimination of toxic compounds, drugs, and their metabolites
Each kidney is divided into a cortex and a medulla, both parts containing
nephrons (approx. 1.25 million per kidney)
Fluid that exits a nephron flows out papilla of a pyramid (8-15 per medulla),
enters a minor calyx, joins effluent of other minor calyces in major calyx, and
is eliminated as urine through ureter
Marc Imhotep Cray, M.D. 14
Functions of Kidneys
Kidneys perform a host of functions (5), including:
Most nephrons originate in kidney cortex, are short, and extend only to
outer medullary zone
23
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014
Blood Vessels Surrounding Nephrons
Critical to multiple kidney functions is close association of nephrons
with blood vessels water and other substances pass from nephron to
blood and vice versa
Contrastly;
Neurotransmitters, drugs, and environmental factors that
constrict afferent arteriole or relax efferent arteriole reduce GFR
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition.
Marc Imhotep Cray, M.D. Saunders, 2014
26
Microscopic Anatomy: The glomerulus
Glomerulus is an important interface between afferent arteriolar
blood flow and nephron
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
Microscopic Anatomy: Tubular Segments
Structure and function of tubular segments are important for
understanding drug effects on kidney
Cl− and other ions move by cotransport with Na+ or other ions
or by passive diffusion
HCO3− and Cl− are most relevant ions for class of diuretic drugs
known as carbonic anhydrase inhibitors
Several diuretics and other drugs cause excess urinary K+ loss as a side
effect
by increasing distal tubular flow rate and Na+ delivery (eg, ethacrynic acid and
furosemide)
by alkalinizing distal tubular fluid (eg, carbonic anhydrase inhibitors such as
acetazolamide), or
by blocking tubular K+ reabsorption (eg, ouabain)
Some diuretics, known as potassium-sparing diuretics, do not cause K+
loss Cray, M.D.
Marc Imhotep 39
Renal Physiology: Fluid compartments
“HIKIN”: HIgh K+ INtracellularly
60–40–20 rule (% of body weight for
average person):
60% total body water
40% ICF
20% ECF
Plasma volume can be measured by
radiolabeling albumin
Extracellular volume can be
measured by inulin or mannitol
Osmolality = 285–295 mOsm/kg H2O
Le T and Bhushan V. First Aid for the USMLE Step 1 2016. NY, New York: McGraw-
Hill Education, 2016.
Practical Application: Measuring
Glomerular Filtration Rate (GFR)
GFR is an important characteristic of normal kidney functioning
and an important variable in elimination of drugs and their
metabolites
In general, greater GFR is, greater rate of elimination is
Marc Imhotep Cray, M.D. Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014 43
Renal Clearance Principle
“Clearance” describes volume of plasma that is cleared of a substance
per unit time
Cx = clearance of X (mL/min).
Ux = urine concentration of X (eg, mg/mL).
Px = plasma concentration of X (eg, mg/mL).
V = urine flow rate (mL/min).
Modified from: Pollock CA, Harris D, & Field MJ. The Renal System: Basic Science and Clinical
Conditions 2nd Ed. Elsevier, 2010
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014
Marc Imhotep Cray, M.D. Burtis CA, Ashwood, ER & Bruns DE. Tietz Textbook of Clinical Chemistry 69
and Molecular Diagnostics, 5th Ed, Saunders, 2012.
Renin-Angiotensin-Aldosterone System Capsule
Le T and Bhushan V. First Aid for the USMLE Step 1 2016. NY, New York: McGraw-Hill Education, 2016.
RAAS Capsule (2)
Renin Secreted by JG cells in response to ↓renal arterial
pressure and renal sympathetic discharge (β1 effect)
AT II Affects baroreceptor function; limits reflex bradycardia,
which would normally accompany its pressor effects
Helps maintain blood volume and blood pressure
ANP, BNP Released from atria (ANP) and ventricles (BNP) in
response to ↑volume; acts as a “check” on RAAS; relaxes
vascular smooth muscle via cGMP ↑ GFR, ↓renin
Dilates afferent arteriole, constricts efferent arteriole, promotes
natriuresis
ADH Primarily regulates osmolarity; also responds to low blood
volume states
Aldosterone Primarily regulates ECF volume and Na+ content;
responds
Marc Imhotep Cray, M.D. to low blood volume states
See next slide for sources and links further study.
Marc Imhotep Cray, M.D. 72
Sources and further study:
eLearning
Renal cloud folder tools and resources
MedPharm Guidebook:
Unit 9 Drugs Used to Affect Renal Function
Renal Pharmacology eNotes
Clinical Pharmacology Cases 7, 8, & 55 (Learning Triggers)
Textbooks
Brunton LL, Chabner BA , Knollmann BC (Eds.). Goodman and Gilman’s The Pharmacological
Basis of Therapeutics. 12th ed. New York: McGraw-Hill, 2011
Katzung, Masters, Trevor. Basic and Clinical Pharmacology, 12th ed. New York: McGraw-Hill,
2012
Mulroney SE. and Myers AK. Netter's Essential Physiology. Philadelphia: Saunders, 2009
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition.
Philadelphia: Sanders, 2014
Toy E C. et.al. Case Files-Pharmacology Lange 3rd ed. New York: McGraw-Hill 2014.
Marc Imhotep Cray, M.D. 73