Renal system

Primary kidney functions

Retain as close to 100% of caloric nutrients as possible by returning them to the blood

Regulate MAP, fluid volume, pH, salt concentration (minerals, H₂O, vitamins (Non-caloric nutrients)) to maintain homeostatic levels; eliminate the excess

Excrete as close to 100% toxins/waste products into urine as possible

GFR

Glomerular filtration rate; about 180L/day. 177L return to the blood; 3L excreted as urine. GFR is high (180 even though we only lose 3) because the kidneys are constantly sampling the blood to monitor levels of non-caloric nutrients and respond accordingly.

Nephron

Functional unit of kidney, ~1 million in average kidney. Filters fluid from blood at the glomerulus and selectively reabsorbs fluids & nutrients as needed in renal tubules connected to it. Fluids/solutes still present at the end of the collecting duct will be discarded as urine through calyces to the ureter.

Glomerulus

Ball of capillaries from renal artery (specifically afferent arteriole), capillaries have fenestrations that filter by size so larger molecules like red blood cells or whole proteins remain in the blood and leave through the efferent arteriole. filtrate (fluid removed from capillaries) is directed to the PCT (proximal convoluted tube). Also has podocytes that form filtration slits with their membranes.

Glomerular capillary

has fenestrations that filter molecules by size; can be stretched out (kidney damage) allowing too large of molecules through (protein in blood); fenestrations covered by podocytes that form slits with their membrane (between foot processes)

Nephron Loop

Blood from glomerulus and then proximal convoluted tubule enters Nephron loop into the thin descending limb over and up the thick ascending limb within the medulla, ascending limb connects to the distal convoluted tube in the cortex that empties into the collecting duct. Fluids and nutrients are reabsorbed throughout this journey until the end of the collecting duct.

Glomerular pressure & regulation

Net Filtration Pressure regulates GFR; Sum of: Blood hydrostatic pressure into glomerulus, capsule hydrostatic pressure out of the glomerulus, and osmotic pressure out of the glomerulus. Vasodilation of the afferent arteriole increases local pressure by letting more blood and fluid into the glomerulus, increasing fluid volume. Vasoconstriction of the afferent arteriole decreases local pressure by preventing more blood and fluid from entering the glomerulus. Works like a water balloon on a faucet.

Autoregulation of GFR

Regulation of GFR in the kidney by the kidney, triggered by high or low MAP. Myogenic and tuboglomerular responses

Myogenic response

Decreased MAP lowers pressure in aterioles and GFR → receptors of smooth muscle detect decreased stretch → afferent arterioles vasodilate to increase local pressure in glomerulus and raise GFR

or

Increased MAP increases pressure in arterioles and GFR → receptors of smooth muscle detect increased stretch → afferent arterioles vasoconstrict to decrease local pressure in glomerulus and lower GFR

Tuboglomerular mechanism

Decreased MAP decreases GFR → decreased filtrate flow and NaCl in ascending limb of nephron loop → macular densa cells in juxtaglomerular complex sense low NaCl levels → vasodilation of afferent arterioles → increased GFR

or

Increased MAP increases GFR → increased filtrate flow and NaCl in ascending limb of nephron loop → macular densa cells in juxtaglomerular complex sense high NaCl levels → vasoconstriction of afferent arterioles → decreased GFR

NaCl GFR relationship

When NaCl is low, GFR needs to increase with afferent arteriole vasodilation

When NaCl is high, GFR needs to decrease with afferent arteriole vasoconstrcition

Hormonal regulation of GFR

Indirect regulation of GFR from systemic regulation of MAP. Low BV → Low MAP → granular cells of juxtaglomerular complex of kidney secrete renin → renin forms angiotensin → short term & long term fixes

Angiotensin short term fix

Vasoconstriction of systemic arterioles increases blood pressure; however this does not impact blood volume and increases resistance. Temporary solution until water is consumed and aldosterone can take over.

Angiotensin long term fix

Stimulates aldosterone secretion from adrenal cortex → aldosterone stimulates Na+ reabsorption in DCT → water follows Na+ → water is retained → blood volume increases → MAP increases

Angiotensin secret third effect

Acts on the hypothalamus to increase thirst to increase the amount of water the body can retain

Hydration

Measured in milliosmoles (mOsm); total concentration of salt in blood. Dehydration: high osmolarity (too salty!!!!) Overhydration: low osmolarity (not salty!!!)

Hormonal regulation of GFR

increased BV leads to veinous pressure that increases pre load in the atria; the atria releases ANP in response to increase GFR.

atrial natriuretic peptide

ANP increases GFR by relaxing mesangial (smooth muscle) cells around glomerular capillaries, which increases surface area, increases GFR, and increases urine formation, all of this lowering blood volume and MAP, the atria’s initial goal

Low BV/MAP

Use angiotensin for systemic vasoconstriction to increase MAP and aldosterone to increase Na+ and H₂O reabsorption to increase MAP and BV

High BV/MAP

use ANP to increase GFR and urine output to decrease MAP/BV

High osmolarity/Dehydration

Use ADH to increase aquaporins in CD to increase H₂O reabsorption and decrease osmolarity

Net fluid movement

After fluid leaves glomerulus, it may be reabsorbed back into capillary

PCT

has cuboidal epithelium with dense microvilli; used for reabsorption of most of water/solutes that make it into GF; filter in glomerular capsule not good enough to keep all the things we want in the blood and take out things we dont, so PCT must actively pump things we want back into blood; TRANSPORTS H+ INTO RENAL FILTRATE

Descending limb

transitions to simple squamous epithelium, tube permeable to water but not salts, increasing salt in the medulla draws water out of the tube. drawing water out and leaving the rest in means the contents of the tube are becoming concentrated at tbe bottom of the loop

Ascending limb

transitions back to cuboidal epithelium; whole purpose of loop is to create a large salt gradient in medulla; ascending loop actively pumps salts out into medulla so the fluid in the tube is less concentrated than the fluid in the medulla; maintains the gradient

DCT

epithelium is cuboidal, no microvilli, several hormones (aldosterone (Na+) and PTH (Ca²⁺)) target cells to fine tune salt/mineral levels; aldosterone stimulates NaCl reabsorption for water to follow sodium (as per hormonal/systemic indirect regulation of GFR); PTH stimulates Ca²⁺ reabsorption

Collecting duct

Continues Na+ and K+ regulation, major site of water regulation by ADH: adh controls aquaporin levels in collecting duct membrane, large salt gradient allows this, gradient peaks at 1200 so urine can be no more concentrated, anything more concentrated must be diluted

Urea

Major nitrogenous waste product; mostly formed by protein metabolism when the liver uses amino acids to make atp; used to establish protein needs; contributes to concentration gradient in medulla along with sodium (if it were just sodium it would be toxic)

pH regulation

blood buffer hides H+ but cannot make long term change; PCT contains H+ pumps that actively transport protons from blood into the renal filtrate, permanently removing protons and restoring pH. This is why urine is usually acidic

Renal clearance

way we can check kidney function; individual injected with molecule that can’t be reabsorbed to follow its concentration in blood and in urine (should be mirrored). Renal failure is GFR < 15ml/min and leads to transplant or dialysis

Kidney stones

renal calculi; block ureter and cause pressure and pain; eliminated by shock waves that shatter stones (still painful to pass)