KAAP 310 Unit 3 (only urine)

urinary system

• 2 kidneys

• 2 ureters

• urinary bladder

• urethra

Functions of kidneys

primary function is excretion

1. Blood filtration and excretion of toxic metabolic wastes

2. Regulation of blood volume, pressure, and osmolarity by regulating water output

3. Regulation of electrolyte and acid base balance of body fluids

4. Secretion of erythropoietin - stimulates production of RBCs and supports O₂ carrying capacity of blood

5. Regulation of calcium homeostasis and bone metabolism through calcitriol synthesis

6. Clear hormones and drugs from the blood - limiting their action

7. Detoxification of free radicals

8. Help support blood glucose level through synthesis of glucose from amino acids in cases of extreme starvation

Waste

any substance that is useless to the body or present in excess of the body’s needs

Metabolic waste

waste substance produced by the body

nitrogenous wastes

small nitrogen containing compounds

• the most toxic of our metabolic wastes

• 50% of nitrogenous waste is urea (byproduct of protein catabolism)

• other nitrogenous wastes include:

  • uric acid- produced by catabolism of nucleic acids

  • creatinine- byproduct of creatine phosphate catabolism

both less toxic than ammonia but must be eliminated due to potential harm

How are nitrogenous wastes created?

1. proteins hydrolyzed into amino acids

2. NH₂ group is removed from each amino acid

3. -NH₂ forms ammonia (exceedingly toxic)

4. Liver converts ammonia to urea (CO(NH₂)₂ (less toxic)

BUN

blood urea nitrogen

• level of nitrogenous waste in the blood

• typical concentration 10-20 mg/dL

azotemia

elevated BUN that can indicate renal insufficiency

• can progress to uremia - syndrome of diarrhea, vomiting, dyspnea, and cardiac arrythmia stemming from the toxicity of nitrogenous wastes

Excretion

process of separating wastes from the body fluids and eliminating them from the body

• carried out by 4 body systems

1. Respiratory

   1. excretes CO₂, small amounts of other gases, and water

2. Intergumentary

   1. excretes water, inorganic salts, lactate, and urea in sweat

3. Digestive

   1. eliminates food residue

   2. excretes water, salts, CO₂, lipids, bile pigments, cholesterol, and other metabolic wastes

4. Urinary

   1. excretes a broad variety of metabolic wastes, toxins, drugs, hormones, salts, H⁺, and water

Gross anatomy of kidney

• lateral surface is convex

• medial surface is concave with a slit (hilum)

hilum

admits renal nerves, blood vessels, lymphatics, and ureter

What layers of connective tissue protect the kidneys

1. renal fascia

   1. immediately deep to the parietal peritoneum

   2. binds kidney and associated organs to abdominal wall

2. perirenal fat capsule

   1. layer of adipose tissue

   2. cushions kidney and holds it in place

3. fibrous capsule

   1. encloses the kidney

   2. protects from trauma and infection

what are the kidneys suspended in?

collagen fibers

renal parenchyma

glandular tissue that forms urine

• C shape in frontal section

• encircles renal sinus

divided into 2 zones divided by the corticomedullary junction

1. renal cortex (outer)

   1. extend into renal columns

2. renal medulla (inner)

   1. divided into renal pyramids

      1. bases of pyramids face cortex

      2. blunt point of pyramids (renal papilla) face the sinus

renal sinus

• cavity occupied by blood and lymphatic vessels, nerves, and urine-collecting structures

• adipose tissue fills remaining space

minor calyx

• surrounds papilla of each renal pyramid

• collects urine

• combine with 1-2 others to form major calyx

• 2-3 major calyces converge in sinus to form renal pelvis

ureter

tubular continuation of the renal pelvis that drains the urine down to urinary bladder

glomerulus

spheroidal mass of blood capillaries in the kidney that filters plasma and produces glomerular filtrate - further processed into urine

how much blood do kidneys receive in a minute?

1.1 L

• 21% of cardiac output - renal fraction

  • mostly meant to remove waste than to meet kidney tissue’s metabolic demands

Circulation to Kidneys

• a renal artery supplies each kidney

aorta → renal artery → segmental artery → interlobar arteries → arcuate arteries → cortical radiate (interlobular) arteries →

• finer branches

→ afferent arterioles → glomerulus → efferent arteriole → (mostly) peritubular capillaries/(1-2%)vasa recta →

• veins

→ cortical radiate (interlobular) veins → arcuate veins → interlobar veins → renal vein → inferior vena cava

renal tubule

• reabsorbs most of water and solutes that filter out of the blood at the glomerulus

• returns them to the bloodstream through network peritubular capillaries around the nephron

vasa recta

network of vessels that supply 1-2% of total renal blood flow to the renal medulla

• its capillaries carry away water and solutes reabsorbed by the sections of the tubule they’re at

how many nephrons does each kidney have?

1.2 million wow

parts of a nephron

1. renal corpuscle - filters blood plasma

2. renal tubule - converts filtrate to urine

Renal Corpuscle

consists of glomerulus and the glomerular capsule that encloses it

• parietal (outer) layer - simple squamous

• capsular space - filtrate collecting separation

• visceral (inner) layer - podocytes wrapped around capillaries of glomerulus

glomerular capsule

double walled capsule around each glomerulus of the kidney

• receives glomerular filtrate and empties into the proximal convoluted tubule

vascular pole

afferent arteriole enters capsule

• brings blood to glomerulus

efferent arteriole leaves capsule and carries blood away

urinary pole

parietal wall of capsule turns away from the corpuscle and gives rise to renal tubule

• simple squamous epithelium of capsule turns simple cuboidal in tubule

mesangial cells

pack spaces among capillaries of glomerulus

• physically support capillaries

• aid in regulating glomerular blood flow

• phagocytize tissue debris

• prevent clogging of glomerular filtration membrane

renal tubule

duct that leads away from the glomerular capsule and ends at the tip of a medullary pyramid

• divided into 4 regions

1. proximal convoluted tubule - part of nephron

2. nephron loop - part of nephron

3. distal convoluted tubule - part of nephron

4. collecting duct - receives fluid from many neprhons

proximal convoluted tubule (PCT)

longest and most coiled of the four regions

• arises from the glomerular capsule

• simple cuboidal epithelium with prominent microvili (a lotta absorption)

nephron loop

long U-shaped portion of renal tubule found mostly in the medulla

• descending limb

  • begins where PCT straightens out and dips toward/into the medulla

• ascending limb

  • returns to cortex and travels parallel to descending

• thick segments

  • simple cuboidal epithelium

  • initial part of descending and all of ascending

  • heavily engaged in active transport of salts (high metabolic activity & loaded w/ mitochondria)

• thin segments

  • simple squamous epithelium

  • forms most of descending limb

  • low metabolic activity

  • very permeable to water

distal convoluted tubule (DCT)

begins shortly after the ascending limb reenters the cortex

• shorter and less coiled

• cuboidal epithelium

• nearly devoid of microvili

• end of nephron

collecting duct

receives fluid from DCTs of several nephrons as it goes back into the medulla

• converge toward tip of a medullary pyramid, and near the papilla they form a papillary duct

• simple cuboidal epithelium

papillary ducts

end in pores at the conical tip of each papilla

• urine drains from these pores into minor calyx that encloses papilla

• simple cuboidal epithelium

flow of fluid from where glomerular filtrate is formed to urine

glomerular capsule → proximal convoluted tube → nephron loop → distal convoluted tube → collecting duct → papillary duct → minor calyx → major calyx → renal pelvis → ureter → urinary bladder → urethra

juxtamedullary nephrons

close to the medulla

• very long nephron loops that extend as far as the apex of renal pyramid

• 15% of all nephrons - major contributors to maintenance of osmotic gradient in medulla

cortical nephrons

farther from medulla

• relatively short nephron loops that dip only slightly into the outer medulla before turning back

• turn back even before leaving the cortex

• some have no nephron loops at all

why are nephron loops important?

maintain osmotic gradient in medulla that helps the body conserve water

• juxtamedullary nephrons huge contributors

Renal plexus

nerves and ganglia wrapped around each renal artery

• issues nerve fibers to blood vessels and convoluted tubules of nephrons

carries:

• sympathetic innervation from abdominal aortic plexus

• afferent pain fibers

role of sympathetic fibers in renal innervation

• stimulation by sympathetic fibers of renal plexus reduces glomerular blood flow, and consequently urine production

• respond to falling blood pressure by stimulating kidneys to secrete renin - enzyme that activates hormonal mechanisms for restoring blood pressure

renin

enzyme that activates hormonal mechanisms for restoring blood pressure

parasympathetic innervation in kidneys

• arise from vagus nerve

• function unknown

Stages of Kidney converting blood plasma to urine

1. glomerular filtration

2. tubular reabsorption

3. tubular secretion

4. water conservation

glomerular filtrate

fluid in capsular space

• similar to blood plasma except that it has almost no protein

tubular fluid

fluid from proximal convoluted tubule through distal convoluted tubule

• differs from glomerular filtrate because of substances removed/added by tubule cells

urine

once fluid enters the collecting duct

• undergoes little alteration beyond this point except for change in water content

glomerular filtration

process in which water and some solutes in blood plasma pass from capillaries of glomerulus into capsular space of the nephron

• has to pass through filtration membrane (3 barriers)

1. fenestrated endothelium of capillary

2. basement membrane

3. filtration slits

fenestrated endothelium of capillary

endothelial cells of glomerular capillaries are honeycombed with large filtration pores

• highly permeable

• pores small enough to exclude blood cells from filtrate

basement membrane

consist of a proteoglycan gel

• a few large molecules may penetrate small spaces and cross

  • most would be held back (larger than 8 nm)

• negatively charged smaller molecules can be held back by negative charge on proteoglycans through repulsion

protein composition of blood plasma and glomerular filtrate

blood plasma - 7%

glomerular filtrate - 0.03% (traces of albumin and smaller polypeptides)

filtration slits

podocyte of glomerular capsule with a bulbous cell body and several thick arms

• each arm has foot processes that wrap around capillaries and interdigitate with each other

• create negatively charged filtration slits that are an additional obstacle to large anions

what molecules can pass freely through the filtration membrane into the capsular space

almost any molecule smaller than 3 nm can pass freely and appear in the urine

• water

• electrolytes

• glucose

• fatty acids

• amino acids

• nitrogenous wastes

• vitamins

these have about the same concentration in glomerular filtrate as blood plasma

• some solutes of low molecular weight are retained in blood stream due to their binding to plasma proteins that can’t pass through membrane

what can allow albumin or blood cells to filter through?

damage to the filtration membrane

• kidney infections

• trauma

strenuous exercise

• reduces perfusion of kidneys

  • deteriorates glomerulus due to hypoxia

    • leaks protein/blood into filtrate

proteinuria (albuminuria)

presence of albumin in urine

hematuria

presence of blood in urine

Filtration pressure

blood hydrostatic pressure (BHP) ~60 mm Hg

• results due to size difference between afferent and efferent arteriole

  • glomerulus has a large inlet and small outlet

hydrostatic pressure in capsular space ~18 mm Hg

• results from high rate of filtration and continual accumulation of fluid in capsule

colloid osmotic pressure (COP) ~32 mm Hg

glomerular filtrate = almost protein free and no significant COP

net filtration pressure (NFP) in kidneys

60_out - 18_in - 32_in = 10 mm Hg

why do glomerular capillaries absorb little to no fluid?

Although BHP also drops throughout course of glomerular capillaries, it is still high enough to solely engage in filtration

hypertension

high blood pressure in glomeruli increase vulnerability to hypertension

• ruptures glomerular capillaries - scarring the kidneys (nephrosclerosis)

• promotes atherosclerosis of blood vessels (including renal)

  • diminishes renal blood supply

• over time this often leads to renal failure, leading to more hypertension and initiating a positive feedback loop

Glomerular filtration rate

amount of filtrate formed per minute by the 2 kidneys combined

• for every 1 mm Hg of net filtration pressure, a young adult male’s kidneys produce ~12.5 mL of filtrate per minute = filtration coefficient (K_f)

GFR = NFP x K_f

filtration coeeficient (K_f)

depends on permeability and surface area of filtration barrier

• 10% lower in women than in men

glomerular filtration rates in humans

males: 180 L/day

females: 150 L/day

what happens when GFR is too high?

fluid flows through the renal tubules too rapidly for them to reabsorb the usual amount of water and solutes

• urine output rises and creates a threat of dehydration and electrolyte depletion

what happens when GFR is too low?

fluid flows sluggishly through the tubules

• gomeruli reabsorb wastes that should be eliminated in the urine

• azotemia may occur

how to adjust GFR quickly

• change glomerular blood pressure

• done through 3 mechanisms:

  • renal autoregulation

  • sympathetic control

  • hormonal control

Renal autoregulation

ability of nephrons to adjust their own blood flow and GFR without external (nervous or hormonal) control

• enables them to maintain a relatively stable GFR in spite of changes in arterial blood pressure

• ensures stable fluid and electrolyte balance despite the many circumstances that substantially alter one’s blood pressure

2 mechanisms of autoregulation

• myogenic mechanism

• tubuloglomerular feedback

myogenic mechanism

stabilizes GFR based on the tendency of smooth muscle to contract when stretched - blood flow and filtration remain fairly stable

1. when arterial blood pressure rises - stretches afferent arteriole

2. arteriole constricts and prevents blood flow into glomerulus from changing drastically

1. when arterial blood pressure falls - afferent arteriole relaxes

2. allows easier blood flow into glomerulus

tubuloglomerular feedback

mechanism by which the glomerulus receives feedback on the status of the downstream tubular fluid and adjusts filtration to regulate:

• its composition

• stabilize nephron performance

• compensate for fluctuations in blood pressure

involves juxtaglomerular apparatus, macula densa, and granular cells

juxtaglomerular apparatus

found at very end of nephron loop, where it reenters renal cortex

• loop contacts afferent and efferent arterioles at the vascular pole of the renal corpuscle

macula densa

patch of slender, closely spaced sensory cells on one side of the loop

• where tubuloglomerular feedback begins

• cells absorb Na⁺, K⁺, and Cl^-; water follows osmotically

  • cells swell and secrete ATP from basal surfaces

  • ATP metabolized into adenosine by mesangial cells

    • stimulates granular cells

granular (juxtaglomerular) cells

modified smooth muscle cells wrapped around the afferent arteriole and to a lesser extent the efferent arteriole

• stimulated by adenosine created by macula densa

• respond to rising adenosine levels by constricting the afferent arteriole

• reduces blood flow into glomerulus, reducing GFR and completing negative feedback loop

mesangial cells may also contract - constricting glomerular capillaries and reducing filtration

basic steps of going from high to reduced GFR

high GFR

1. increased NaCl load in nephron loop

2. macula densa secretes ATP

3. mesangial cells metabolize ATP to adenosine

4. adenosine stimulates granular cells

5. afferent arteriole constricts

reduced GFR

how does the tubuloglomerular feedback process affect the distal convoluted tubule?

distal convoluted tubule has a limited capacity for NaCl reabsorption

• tubuloglomerular feedback process helps prevent overloading the distal convoluted tube with NaCl

  • preventing excessive NaCl and water loss in urine

what is an additional effect of granular cells?

their granules release renin in response to blood pressure, which initiates a renin-angiotensin-aldosterone mechanism

• contributes to the restoration of blood pressure and supporting blood volume

2 important things to keep in mind about renal autoregulation

1. doesn’t completely prevent changes in GFR

   1. maintains dynamic equilibrium - fluctuates within narrow limits

2. changes in BP do affect GFR and urine output

   1. can’t compensate for extreme BP variations

      1. GFR remains stable within a range of 90-180 mm Hg

      2. Below 70 mm Hg - glomerular filtration and urine output cease (hypovolemic shock)

Sympathetic control of glomerular filtration

sympathetic stimulation and adrenal epinephrine constrict afferent arterioles

• reduces GFR and urine output while redirecting blood from kidneys to heart, brain, and skeletal muscles (where it is more urgently needed)

Renin-Angiotensin-Aldosterone Mechanism

1. substantial drop in BP detected by baroreceptors in aorta and carotid arteries

2. transmit a signal to the brainstem, leading to various corrective sympathetic reflexes

3. sympathetic fibers stimulate granular cells to secrete renin

4. renin acts on angiotensinogen (protein in blood plasma) to split off a 10 amino acid peptide called angiotensin I

5. in the lungs and kidneys, angiotensin converting enzyme (ACE) removes two more amino acids → converting it to angiotensin II

6. angiotensin II restores fluid volume and blood pressure

angiotensin II (a baddie) and her impact

leads to effects that rise blood pressure through water loss, encouraging water intake, and constricting blood vessels

• potent vasoconstrictor

  • widespread vasoconstriction raises the mean arterial BP throughout body

• in kidneys, constricts efferent arterioles less than afferent

  • raises glomerular BP and GFR - target is to prevent drastic reduction in GFR

  • ensures continued filtration of wastes from blood even w/ low BP

    • constriction of efferent arterioles lowers BP in peritubular capillaries downstream - strongly enhances reabsorption of NaCl and water from nephron - returning it to bloodstream instead of losing it in urine

• stimulates the adrenal cortex to secrete aldosterone

  • promoting sodium and water reabsorption by distal (and proximal) convoluted tubule and collecting duct

• stimulates posterior pituitary to secrete antidiuretic hormone

  • promotes water reabsorption by collecting duct

• stimulates sense of thirst and encourages water intake

the birth and legacy of angiotensin II

• Liver gives us angiotensinogen

• when kidney senses drop in blood pressure it tells renin to chop up angiotensinogen to get angiotensin I

• angiotensin I lowkey just angiotensin II before glam

• it goes to the dressing rooms in the lungs and kidneys, gets even more snatched using ACE, and steps outside:

  • angiotensin II hits the hypothalamus and suddenly everyone is thirsty and drinking

  • in the cardiovascular system angiotensin II makes everyone feel like they have to suck in, causing vasoconstriction

  • when it goes to the adrenal cortex it tells aldosterone to pop out and suddenly all the sodium and water don’t wanna leave

• angiotensin II told everyone to step it up, increasing blood pressure all over the body

proximal convoluted tubule

• reabsorbs ~65% of glomerular filtrate

• removes some substances from the blood and secretes them into the tubule for disposal in the urine

• great length and prominent microvili = absorptive surface area

• abundant large mitochondria = provide ATP for active transport

tubular reabsorption

process of reclaiming water and solutes from the tubular fluid and returning them to the blood

• PCT reabsorbs greater variety of chemicals than any other part of nephron

• 2 routes of reabsorption

1. Transcellular route

2. Paracellular route

transcellular route

involved in tubular reabsorption

• substances pass through the cytoplasm and out the base of epithelial cells

paracellular route

involved in tubular reabsorption

• substances pass through gaps between cells

water movement in tubular reabsorption

tight junctions between epithelial cells are leaky and allow significant amounts of water to pass through

• involves solvent drag - as water travels through epithelium, it carries a variety of dissolved solutes

direction of movement of water and solutes

enter tissue fluid at base of epithelium, and are then taken up by the peritubular capillaries

Sodium Chloride in tubular reabsorption

important for all aspects as it creates an osmotic and electrical gradient, which drives reabsorption of water and other solutes into epithelial cells

• most abundant cation in the glomerular filtrate

• 2 types of transport proteins that drive sodium uptake

1. Symports

2. Na⁺-H⁺ antiport

Symports and Sodium Chloride

simultaneously bind Na⁺ and another solute (glucose, amino acids, lactate)

• dont consume ATP

• considered secondary active transport because of dependence on Na⁺-K⁺ pumps at the base of the cell

Na⁺-H⁺ antiport and Sodium Chloride

pulls Na⁺ into the cell while pumping H⁺ out of the cell into the tubular fluid

• reabsorbs sodium

• eliminates acid from body fluids

• activated by angiotensin II - exerts strong influence on sodium reabsorption

ATP consuming active transport pump

how is sodium accumulation in epithelial cells prevented?

1. Na⁺-K⁺ pumps in the basal domain of plasma membrane pump Na⁺ out into the extracellular fluid

   1. (ATP consuming active transport pumps)

2. Na⁺ picked up by peritubular capillaries and returned to the bloodstream

3. Cl^- ions follow Na⁺ due to electrical attraction

4. Various antiports in the apical cell membrane absorb Cl^- in exchange for other anions that they eject into the tubular fluid

5. Cl^- and K⁺ ions are driven out through the basal cell surface by a K⁺-Cl^- symport

6. Na⁺ and Cl^- pass through tubule epithelium by paracellular route between cells

Which ions pass through paracellular route with water?

1. phosphate (also cotransported into epithelial cells with Na⁺)

2. magnesium

3. potassium

4. Calcium

   1. 52% reabsorbed by paracellular route (PCT)

   2. 14% reabsorbed by transcellular route (PCT)

      1. reabsorption not dependent on hormones in PCT

   3. 33% reabsorbed in nephron (parathyroid influence)

   4. 1% excreted in urine

glucose in tubular reabsorption

cotransported with Na⁺ by sodium-flucose transporters (SGLTs) symports

• removed from basolateral surface of cell by facilitated diffusion

• normally all glucose is reabsorbed

Nitrogenous wastes in tubular reabsorbption

urea passes through epithelium with water

• 40-60% of urea in tubular fluid reabsorbed by nephron

  • also reabsorbs 99% of water, increasing urea concentration in blood/glomerular filtrate

• kidney removes about half of the urea in the blood to keep concentration at a safe level

uric acid mostly reabsorbed by PCT

• later parts of nephron secrete it back into tubular fluid

creatinine

• not reabsorbed - stays in tubule and passes in urine

water in tubular reabsorption

2 thirds of water is reabsorbed by PCT

• kidneys reduce 180 L of glomerular filtrate to 1 or 2 L of urine each day

reabsorption of all solutes makes tubule cells and tissue fluid hypertonic to tubular fluid

• water follows solutes by osmosis through paracellular and transcellular routes

movement of water in tubular reabsorption

follows solutes by osmosis through paracellular and transcellular routes

transcellular absorption

• occurs through aquaporins in apical and basolateral domains of plasma membrane

• emables water to enter tubule cells at the apical surface and leave them (to return to the blood) via the basolateral surface

reabsorption proportions in tubular reabsorption

• PCT reabsorbs proportionate amounts of solutes and water

• Elsewhere in the nephron, water reabsorption varies due to influence of hormones responding to body’s state of hydration

obligatory water reabsorption

Absorption of water at a constant rate in the PCT

Uptake by peritubular capillaries

after water and solutes leave basal surface of tubule epithelium, they reabsorbed by peritubular capillaries

• 2 mechanisms:

1. osmosis

2. solvent drag

what factors promote osmosis into peritubular capillaries

1. Creation of a high tissue fluid pressure through accumulation of reabsorbed fluid on the basal side of epithelium - physically drives water into capillaries

2. Narrowness of efferent arteriole decreases resistance to reabsorption - lowers BHP from 60 mm Hg in glomerulus to 8 mm Hg in peritubular capillaries

3. Protein being retained as water is filtered out when blood passes through the glomerulus - elevates blood’s COP when it leaves the glomerulus

high COP and low BHP in capillaries + high hydrostatic pressure in tissue fluid = balance of forces in peritubular capillaries → favor reabsorption

bonus factor:

• angiotensin II constricts afferent and efferent arteriole, reducing blood pressure in peritubular capillaries and reducing resistance to fluid reabsorption

steps of uptake by the peritubular capillaries

1. Angiotensin II secreted

2. constricts afferent and especially efferent arterioles

3. Maintains glomerular blood pressure and glomerular filtration

4. reduces blood pressure in peritubular capillary

5. reduces resistance to tubular reabsorption

6. tubular reabsorption increases

7. urine volume is less but concentration is high