Anatomy Ch 26

• 1. Ion (electrlyte) regulation - secretion & reabsorption
• 2. pH regulation - H⁺, HCO_3-
• 3. BP & Blood volume regulation - renin/ angiotensin/ aldosterone system and ADH
• 4. osmolarity regulation - blood/ solutes
• 5. hormone production - renin, erythropoietin
• 6. glucose regulation - reabsorption called "gluconeogenesis"
• 7. excreation of waste products
• - NH₃(amonia)/ Urea - protein breakdown
• - bilirubin - Hgb breakdown
• - creatine - creatine P breakdown
• - uric acid - DNA/RNA breakdown
• - drugs
• - toxins

• Urine is form in the nephron
• Nephron→ collecting duct → minor calyx→ major calyx → renal pelvis → ureter → bladder → urethra

• 25% of cardiac output (1.25 lt/ min)
• Aorta →
• Descending aorta →
• Renal arteries (L and R) →
• Segmental arteries →
• Interlobular arteries→
• Arcuate arteries (between cortex/ medulla)→
• Interlobular arteries→
• (Produce filtrate):
• afferent arteriole →
• glomerular capillary →
• efferent arteriole →

• nourish nephron:
• peritubular capillary (around) →
• or vasa rects (parallel to loop)→
• peritubular venules→
• interlobular veins→
• arcuate veins→
• interlobar veins→
• segmental veins→
• Renal veins (R and L)→
• IVC→
• RA

• ANS - Sympathetic motor - supplies vasomotor input to afferent arterioles -
• sympathetic stimulation = renal arteriolar vasoconstriction

Hypothalamus → spinal cord→ celiac ganglion→ renal plexus →afferent arteriole

Nephrons are located in the cortex but the loop of Henle dips down into the renal medulla.

• Two types of loop:
• 1. Short loop nephrons (85%) are located in the cortex and loop is shallow in the medulla
• 2. Long loop nephrons (15%) are located in the juxtamedullary (next to medulla) and the loop goes deep into the medulla
• - long loops have thick and thin ascending
• - can produce very concentrated urine

• Proximal tubules = cortex
• Distal tubules = cortex
• Collecitng duct = extend from cortex through the medulla to the renal pelvis

• A nephron has various types of cells throughout its system.
• Several nephrons will empty into the same collecting duct

The vasa recta is a group of capillaries parallel to the loop of Henle. They come off the efferent arteries and they recombine with the peritubular arteries at the peritubular venules

Normal cardiac output = 1250 cc/ min (1.25 lt/ min)

Normal GFR = 125 cc/ minute

Urine output/ hour = 60 cc/hr

• Urine output/ minute = 1 cc/min
• of 125cc filtered/ min only 1cc is urine - 99% of filtrate is reabsorbed

20% - called the filtration fraction

99% of filtrate is reabsorbed

• The glomerulus a high pressure "capillary-like" ball - not capillaries becuase it is between two arterioles (not arterioe to venule)
• afferent arteriole →glomerulus → efferent arterioles

• Plasma is pushed through a filtration membrane:
• 1. fenestrated entothelium (innermost)
• 2. basal lamina (CT)
• 3. Filtration slit membrane - Between the pedicels of visveral podocytes are slits with a thin slit membrane over them.

Mesangeal cells are between & around the capliiaries and control the surface area of the capillaries. When the mesangeal cells are relaxed the surface area is maximal. When mesangeal cells contract the surface area decreases as does filtration.

1. Visceral layer - simple squamous with podocytes that wrap around the capillaries.

2. Parietal layer - simple squamous - out layer of capsule

3. Bowmans space - between the two layers - filtrate from the glomerulus goes here.

Simple cuboidal with microvilli (brush border) to increase surface area.

• Descending loop= simple squmous
• Thin ascending loop = simple squamous
• (impermeable to H₂O)
• Thick ascending loop = simple cuboidal or columnar
• (short loop nefrons don't have thin ascending).

Macula densa = where the ascending limb makes contact with the afferent arteriole serving the renal corpuscle - columnar tubule cells are crowded together

Juxtaglomerular cells - smooth muscle fibers alongside the macula densa on the wall of the afferent arteriole. They secrete renin.

JGA - juxtaglomerular apparatus - the macula densa and juxtaglomerular cells - regulates BP in the kidneys - regulates renin output which controls H₂O, Na,& K through the renin/ angiotensin/ aldosterone pathway.

• Principal cells are found in the DCT and collection duct.
• They have receptors for ADH and aldosterone.
• Regulate H₂O, Na^₊, K+, HCO_3-

• In the collection duct.
• They regualte pH via
• H⁺ secretion
• HCO_3- reabsoprtion

• 1. Filtration - H₂O & solutes - in glomerulus- 125cc/min
• 2. Absorption - 99% of filtered H₂O is reabsorbed in tubules- most solutes reabsorbed
• 3. Secreation - remove waste- occurs in tubules

Filtrate is plasma that is pushed through the filtration membrane into Bowman's capsule - 20% of blood flow to kidneys is filtered.

Filtate contain H₂O, Ions, Aura, Anonia, & very small plasma proteins

1. Most important -Increased hydrostatic pressure - arterial system - efferent arteriole (out) has smaller diameter than afferent arteriole (in)

2. Leakiness of glomerular capillary - fenestrated, thin, more pourous

3. Increased surface area- on endthelium - controlled by mesangial cells (relax = ↑ SA)

GCHP - Glomerular capillary hydrostatic pressure - drive filtration -55 mm Hg (outward)

CHP- Capsular hydrostatic pressure - opposes filtraion - back pressure of 15 mm Hg

55- (30+15) = 10 mm Hg net pressue outward


BCOP = Blood colloid osmotic pressure - solute in blood plasma makes water want to move back to glomerulus - 30 mm Hg

GFR = 150-180 liters/ day

99% reabsorbed

• Urine output = 1-2 liters/day
• minimum normal = 60 cc/ hour

1. Adjusting blood flow in and out of the glomerulus

2. Adjusting surface area for filtration to occur

Renal autoregulation - the kidneys have the ability to maintain a constant renal blood flow and GFR even when the systemic BP changes.

1. myogenic mechanism - ↑ BP = stretchin of afferent arterioles - triggers contraction of smooth muscle in afferent arteriole = narrows lumen of arteriole - renal BP remains constant

• 2. tubuloglomerular - macula densa provides feedback to glomerulus - If BP is high, filtered fluid flows more rapidly and reabsorption is not complete. Macula Densa denses high H₂O or ions and inhibits the JGA from releasing NO (nitric oxide).
• NO = vasodilator
• less NO = afferent arterioles constrict - less blood flow.

sympathetic nervous system - shunt blood to more vital organs for fight or flight

SNS stimulation (hypotension -low BP) →↑ NOR→ Vasoconstriction → ↓GFR

Angiotensin II and ANP

• Angiotensin II -
• when BP ↓ or Volume ↓ - Angiotensin causes vasoconstriction of both afferent and efferent arterioles
• angiotensin II = decreased GFR

• ANP - atrial natriuretic peptide
• when blood volume ↑ - wall of atria stretch & atria secrets ANP
• - ANP work on mesangeal cell to relax them - glomerular capillaries dilate - SA increases = GFR increases

the return of H₂O & solutes to the blood stream

• 99% of filtrate is reabsorbed
• 65% in the PCT
• 15% in the loop of Henle
• 10% in DCT
• 10% in collection duct

urea and creatinine (all creatinine is secreted)

1. paracellular reabsorption - around the tubule cell - filtrate moves out of the tubule by passively leaking between two cells to interstitial space and to the blood.

2. transcellular reabsorption - through the tubule cell- filtrate enters apical membrane of tubule cell, moves across the cytosol, and out through the basolateral membrane into the interstitial fluid - then to blood

• 1. Diffusion - simple & facilitated
• 2. Osmosis
• 3. Primary active transport - Na+/ K+ ATPase pump
• 4. Secondary active transport - symporters/ antiporters

transport proteins can be overwhelmed and solute will spill into urine (glucose)

Osmosis - H₂O follows solutes - it is reabsorbed passively

Obligatory - 90% of reabsorption -water is oblicated to follow solute

Facultative - 10% of reabsorption - fine tuning in DCT/ collecting duct - with help of ADH

T_max = transport maximum - the amount of substance that can be transported (reabsorbed) by carrier proteins - if T_max is exceeded solute spills into the urine

ex glucose, water soluble vitamins

• 1st half of PCT = active transport (primary or seconday)
• Na+ (primary/ sec) with symporters/ antiporters
• Glucose = Na+ symporter
• HCO₃^_ , H+ secretion

• 2nd half of PCT = passive diffusion
• -all ions (except Na+) and urea (by product of a.a. breakdown)
• osmosis

Osmolarity = total # of dissolved particles/ liter of plasma

2[NA+] + [K+] + [Glucose]/ 18 + [BUN]/ 2.8= ~300 mOsm

normal = 300 mOsm/ liter

Descending limb = permeable to H₂O - impermeable to ions

Ascending limb = Impermeable to H₂O - permeable to ions - has active transport mechanisms for ions (Na+, K+, Cl- symporters)

The active transport of ions into the interstitial space around the loop establishes a gradient for osmosis (lots of Na+ outside the loop = water follows)

• At the beginning of the descending limb the osmolarity of the filtrate is 300 mOsm - same as plasma
• - as water leaves on the way down osmolarity goes up to 1200 mOsm (at bottom of loop)
• - as filtrate goes back up and ions are pumped out the osmotalrity drops to 100 mOsm (less than plasma)

H₂O absortion cannot be coupled with solute reabsorption due to the loop

Solutes are pumped out in the ascending loop which creates a osmotic gradient in the interstitial fluid around the loop - which is what allow water to move out passively in the descending loop.

Principal cells - aldosterone & ADH receptors

• Aldosterone (made in adrenal cortex) stimulates principal cells to reabsorb more Na+ and Cl- and secrete K+
• - Na+ and Cl- reabsorption causes more water to be reabsorbed
• = increased blood volume

ADH = antidiuretic hormone - vasopressin - vasoconstrictor

• Made in the posterior pituitary
• Secreted by the hypothalamus

• Secreted when baroreceptos indicate low PB
• - also when osmoreceptors (in the hypothalamus & pituitary) detect increased osmolarity (more solute in plasma)

• Works on the principal cells (have ADH receptors) in the DCT and collecting duct.
• - stimulates the principal cells to increase H₂O permeability = increased H₂O reabsorption
• - also increases systhesis/ insertion of aquaporins (channel proteins)

ADH = more concentrated urine

Intercalated cells are in the DCT and collecting duct.

• They regulate pH
• -reabsorb HCO_3- (bicarbonate)
• -secrete H⁺
• - reabsorb Ca+ (controlled by PTH)

• 1. Angiotensin II -
• renin (secreted in JGA)/ angiotensin/ aldosterone
• -↓GFR by causing vasoconstrition of afferent arterioles
• - ↑ Na+ & Cl reabsorption by stimulating Na+/ H+ antiporters
• - stimulates adrenal cortex to release aldosterone

• Aldosterone -
• stimulates principal cells to save Na+ & Cl + - throw out K+ (water follows)= increases blood volume

• ADH - anti diuretic hormone- vasopressin
• secretion from hypothalamus (made in post pit) is triggered by low BP (baroreceptors) or high osmolarity (osmoreceptors)
• - increases reabsorption of water

• ANP - atrial naturetic peptide -
• Natriuretic = excretion of Na+ in urine
• -Atrial stretch (increases BP or volume) = atrium secretes ANP -↓ water reabsorption & Na+ reabsorption
• = more dilute urine

Diuretics increase urine output

Increase H₂O, Na⁺, Cl^-, K⁺ loss in unine

• Used to treat edema
• 1. CHF - congestive heart failure - pulmonary edema 2. hypertension - high BP

• Lasix (furosemide) - works at the loop of Henle
• HCTZ (hydrocholrthiazide) - works at distal tubule

• 1-2 liters/ day
• yellow, clear
• pH ~6
• no protein, glucose, microbes, cells
• urine is sterile

• Normal Osm =
• Dilute = 65 mOsm/L
• Concentrated = 1200 mOsm/L

If a patients Osm is always 300 (Osm of blood) they are experiencing renal failure

• 1-2 liters/ day
• 1cc/kg/hour

• Blood tests
• [BUN] = blood urea nitrogen
• urea (a.a) breakdown - indicator of renal function since kidney excretes some urea

• [Cre] = creatinine (creatine P breakdown -muscle)
• better indicator of renal function since kidney excretes all of it - shouldnt be much in blood

• Renal plasma clearance - collect urine for 24 hrs
• -determine amount of cre in it
• - cre is not reabsorbed so all of it should be in the urine

• Ureters:
• Retroperitoneal
• 12" long
• Flow by gravity and peristalsis
• Transitional epithelium (for stretch)

• Bladder:
• storage vessel - about 1 L
• transitional epithelium (stretch)

• When bladder has about 200 ml of urine you get the urge to urinate
• - stretch receptors in bladder signal mictruation center in the spinal cord - urge to urinate registers in the cerebral cortex
• - ANS - parasympathetic motor - spinal reflex arc

External sphincter (urethra) relaxes through voluntary effort

Internal sphincer - relaxes automatically when external one does

• retroperitoneal
• Tissue:
• 1. Mucosa - transitional endothelium - rugae
• 2. Muscularis - detursor muscle (smooth muscle) - ACh stimulates which increases fluid pressure - urge to pee
• 3. Adventitia - loose areolar CT
• 4. Serosa - visceral peritoneum