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List the funcitons of the urinary system.
- 1. Ion (electrlyte) regulation - secretion & reabsorption
- 2. pH regulation - H+, HCO3-
- 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
Draw a picture of a kidney
Draw a close op inside of the kidney
Describe the collection system for urine.
- Urine is form in the nephron
- Nephron→ collecting duct → minor calyx→ major calyx → renal pelvis → ureter → bladder → urethra
Blood supply to the kidney?
- 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)→
What is the nerve supply to the kidney?
- ANS - Sympathetic motor - supplies vasomotor input to afferent arterioles -
- sympathetic stimulation = renal arteriolar vasoconstriction
Hypothalamus → spinal cord→ celiac ganglion→ renal plexus →afferent arteriole
Where in the kidney are most nephrons?
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
Where are the proximal tubules located?
- Proximal tubules = cortex
- Distal tubules = cortex
- Collecitng duct = extend from cortex through the medulla to the renal pelvis
Is a nephron one cell?
Does each nephron have its own collecting duct?
- A nephron has various types of cells throughout its system.
- Several nephrons will empty into the same collecting duct
What is the vasa recta?
Where does it come off?
Where does it go?
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
What is normal cardiac output/ min to the kidneys?
Normal urine output/ hour?
Normal urine output/minute?
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
How much of the cardiac output is filtered by the glomerulus?
How much of the filtrate is reabsorbed?
20% - called the filtration fraction
99% of filtrate is reabsorbed
Describe the make up of the glomerulus.
What cell types facilitate filtration?
How do mesangeal cells work?
- 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.
Describe Bowman's Capsule
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.
What type of cell is in the proximal tubule?
Does the proximal tubule have a brush border?
Simple cuboidal with microvilli (brush border) to increase surface area.
What type of cells are found in the loop?
Where is the macula densa?
Where are juxtaglomerular cells found?
- 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).
= where the ascending limb makes contact with the afferent arteriole serving the renal corpuscle - columnar tubule cells are crowded together
- smooth muscle fibers alongside the macula densa on the wall of the afferent arteriole. They secrete renin.
- juxtaglomerular apparatus - the macula densa and juxtaglomerular cells - regulates BP in the kidneys - regulates renin
output which controls H2
O, Na,& K through the renin/ angiotensin/ aldosterone pathway.
Where are the principal cells found?
What do they regulate?
- Principal cells are found in the DCT and collection duct.
- They have receptors for ADH and aldosterone.
- Regulate H2O, Na+, K+, HCO3-
Where are intercalated cells found?
What do they regulate?
- In the collection duct.
- They regualte pH via
- H+ secretion
- HCO3- reabsoprtion
Name the 3 processes involved in urine formation.
How much of the filtered water is reabsorbed?
- 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
What is filtrate?
What cells are filtered?
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
What 3 characterisitics allow filtration to occur at the glomerulus? (as opposed to elsewhere)
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)
What determines net filtration pressure?
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
How much plasma does the kidney filter/ day?
How much urine is made?
GFR = 150-180 liters/ day
- Urine output = 1-2 liters/day
- minimum normal = 60 cc/ hour
How is GFR regulated?
1. Adjusting blood flow in and out of the glomerulus
2. Adjusting surface area for filtration to occur
What is renal autoregulation?
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
What does reabsorption mean?
the return of H2O & solutes to the blood stream
How much of what's filtered is reabsorbed?
- 99% of filtrate is reabsorbed
- 65% in the PCT
- 15% in the loop of Henle
- 10% in DCT
- 10% in collection duct
What substances are filtered but only partially reabsorbed?
urea and creatinine (all creatinine is secreted)
What are the 2 routes of reabsorption?
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
What are the mechanisma for reabsorption?
- 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)
What is osmosis?
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
What does Tm mean? Why does it occur?
Tmax = transport maximum - the amount of substance that can be transported (reabsorbed) by carrier proteins - if Tmax is exceeded solute spills into the urine
ex glucose, water soluble vitamins
Which half of the proximal tubule does active reabsorption occur? passive?
- 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)
What factors determine osmolarity?
Osmolarity = total # of dissolved particles/ liter of plasma
2[NA+] + [K+] + [Glucose]/ 18 + [BUN]/ 2.8= ~300 mOsm
normal = 300 mOsm/ liter
Where does reabsoprtion occur in the loop of Henle?
What is the osmotic gradient of the loop?
Descending limb = permeable to H2
O - impermeable
Ascending limb = Impermeable to H2
O - 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)
How does the loop independently regulate H2O and osmolarity?
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.
In the distal tubules - where are aldosterone & ADH receptors found?
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
What is ADH?
Where is it made?
What causes its release?
Where does it work?
What does it do?
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
What do intercalated cells do?
Intercalated cells are in the DCT and collecting duct.
- They regulate pH
- -reabsorb HCO3- (bicarbonate)
- -secrete H+
- - reabsorb Ca+ (controlled by PTH)
Explain Hormonal regualtion of reabsorption
4 hormones affect reabsorption.
- 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
What is a diuretic?
What do you lose?
What are they used for?
Diuretics increase urine output
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
Describe normal urine
What if patients mOsm is always 300?
- 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
What is normal urine output?
- 1-2 liters/ day
What is [BUN] and [cre]?
Why are they useful in determining renal funciton?
Why is a 24 hr creatinine clearance a good indicator of renal function?
- 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
- 12" long
- Flow by gravity and peristalsis
- Transitional epithelium (for stretch)
- storage vessel - about 1 L
- transitional epithelium (stretch)
What is the micturation reflex?
Is it autonomic?
Where is the micturation center?
What role does the cerebral cortex play in urination?
- 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
Histology of the bladder
- 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