Renal Physiology

Fnc: removal, acid bade, BP, Vit D, EPO, catabolism of peptide hormones,
metabolism/excretion of xenobiotics
Renal artery interlobar arcuate interlobular affererent glomerular
efferent peritubular some split into vasa recta join back together
interlobular vein arcurate vein interlobar vein
Juxtamedullary nephrons long loops of Henle, vasa recta have a slightly different
function
In a biopsy: needle into kidney some pts may bleed ntetrlobular, arcurate,
interlobar veins cut (capillaries can constrict)
Glomerulus structure and function
o Afferent arteriole splits into 10 20 capillary looms glomerulus
o Surrounded by podocytes around their BM
o Podocytes have primary, secondary and tertiary foot processes that
completely cover the glomeruli
o Podocyte foot processes -> BM -> endothelium
o Small pores in endothelium allows fluid to pass through
o Clinical: disease that attacks podocytes so theyre finger like processes are
further apart (leakage) or fused together (no filtration)
o Endothelial cells important different types of fenestration can be
damaged in severe HTN, diabetes (excessive glucose affects glycolids),
pregnancy
GFR
o 140L passes through per day
o Maintenance of filtration: pressure (oncotic and hydrostatic), blood flow,
permeable capillary wall
o Permeability of membrane decreases (becomes thicker) filtration
decreases proportionally, but once at a certain thickness, plateus
o Beyond a certain pressure, filtration ceases. Need a certain amount to start,
after this rise is proportional. When oncotic pressure rises, a negative force
pulls fluid back into circulation (Starling forces??)
o Normal physiological BP of 120/80 constant GFR
o Lower arterial BP when efferent arteriole too low, afferent constricts
Juxtaglomerular apparatus
o When pressure drops, these cells release chemicals:
Renin acts on angiotensin in bloodstream ACE AT2
vasoconstriction
From macula densa
o When BP drops, JG stimulated to release prostaglandins, NOs etc.
o Intrinsic:
o Myogenic mechanism
o Tubuloglomerlar feedback mechanism
Case: postural hypotension (loss of SNS), no change in creatine
o What factors are maintaining GFR in this man?
o Intrinsic mechanisms if BP too low
o Afferent arterioles contrict myogenic mechanism
o RAAS
 Renal clearance:
o The volume of blood that is completely cleared of a substance every minute,
referred to as GFR
o Insulin clearance measures GFR most accurately as it filtered completely and
nether absorbed nor filtered by the tubules
o Formula urine conc x urine vol over 24hrs/ plasma conc of insulin
Endogenous substances
o Creatine comes from creatine phosphate in muscles
o Early stage of disease: large change in GFR, little in creatine, reverse true in
late stage
o Now more formulas have been developed to measure creatine clearance
(e.g. Swartz formula for children)
Case: 60yo woman has signs and symptoms of UTI high WBC (pyruria)
o Drug dose needs to be altered
Other components of the glomerulus is the podocyte slit diagram
o Nephrin (protein) and collagen maintain the split diagprham integrity
o Intergtins bind podocytes to BM
o Disease of these structures, get leak of proteins
o These proteins are specific to BM
o Can be congentital, sepis
Primary purpose of glomerulus is to generate a protein free filtrate in a steady
fashion 4 factors that regulate
Myogenic, tubuloglomerulic, RAAS
Renal proximal tubule
o Reabsorbs most material thrown out glucose, sodium, proteins,
bicarbonate, organic acid
o High amounts of mitochondria metabolic activity
o High energy requirement driven by Na/K ATPase
o Symport transport
o Bicarb need carbonic anhydrase to be absorbed this splits up into
sodium and bicarb
o Sodium hydrogen exchanger pumps out H+ into the lumen, sodium hydrogen
exchanger
o If carbonic anhydrase is inhibited the carbonic acid coming out the cell is
decreased, increase in bicarb, get acidosis
Glucose reabsorption
o 100% reabsorbed
o Sodium glucose transporter = high efficiency
Case: diabetic pt forgets insulin, high BG will he urinate more or less?
o Glucose reabsorbed with sodium transport
o Water follows, urinate more
Case: 50yo man, obese, has always had sugar in his urine but bl sugar levels,
HbA1C, glucose tolerance test: normal
o He doesnt have diabetes
o Diagnosis glycosuria, problem in PCT, SGLT 2 receptors damaged (not all is
reaborped, spilling over into urine)
Phosphate transport
 o ?
Children with rickets high phosphate excretion due to problem with phosphate
transporter
Glutamine metabolism normally reabsorbed
o Metabolism can change in some situations
o Kidney can produce glucose (gluconeogenis)
o Muscles release glucose into body
o Acidosis e.g. in ketoacidosis
o In mitochondria, glutamine broken to glutamate by ?
o Glutamate is broken down by a-ketog dehdyrongenase to form a-
ketoglutarate
o Converted to oxylaceltate feeds Krebs can genertate ATP, and aslo
generate PPCK (starting point for gluconeogenesis)
o Creatine is freely filtered and secreted
Case: 65YO woman, chemo with cisplatin, low serum bicarb, phosphate and uric
acid. Excess glycosuria, but notmal bl glucose
o Cisplatin affects PCT function get defects in all these absorptions