PHAR 211 Exam 2 (RENAL and HOMEOSTASIS)

Renal Cortex

The outer wall

nephrons found here

blood filtration, urine formation, fluid homeostasis

Renal pyramid

triangles

concentrate urine, maintain salt-water balance, transporting urine to the renal pelvis

Renal column

the little channel spaces in between each triangle

structural support, conduits (channels)

supply blood to the nephrons and urine formation

Renal medulla

nephrons here (in inner medulla)

concentrate urine and maintain body water and electrolyte homeostasis

utilizes loop of Henle

Ureter

Transport tube

primary transport highway for urine from the kidney to the bladder

Renal Sinus

the spaces between the tubes, triangles, and columns

protective, structural, and vascular channel

houses the renal pelvis, calyces, renal artery/veins, nerves, and lymphatic vessels

Renal Pelvis

where all the tubes meet up before moving to the ureter

Funnel shaped reservoir, collects urine from major calyces and directs it to the ureter for transport to the bladder

Major calyces

major channel in the kidneys

collects urine from the minor calyces

directs urine into the renal pelvis

Nephrons

The filtering component of urine

Found in

• Renal cortex (Cortical nephrons)

  • 80-85% of nephrons

• Renal cortex and inner renal medulla (Juxtaglomerular Nephrons)

  • 15-20% of nephrons

Yellow things that have the glomerulus, bowman’s capsule, PCT, loop of Henle, DCT, collecting duct, etc

Urine flow through kidney

Nephrons → pyramids → pelvis → ureter → bladder

Renal Corpuscle

The initial blood-filtering component of the nephron, located in the renal cortex (1 million per kidney)

component’s include:

• Bowman’s capsule

• Glomerulus

• Bowman’s space

• Epithelial layers of nephron

Filtration membrane

Components of the filtration barrier

• Capillary

• Basement membrane

• Podocytes cells processes

Filtration

from glomerulus into bowman’s space

Reabsorption

Back to the blood

ex. glucose needs to go back to the blood

Secretion

From blood to tubule (nephron)

waste products to be excreted into urine

Macula Densa

Located in the DCT

Monitors NaCl concentration of filtrate and BP through osmoreceptors

when NaCl or BP drops, MD cells signals Juxtaglomerular cells to release RENIN

too much NaCl? vasoconstriction to slow down

• MD can also tell JG cells to change its renin release (slow it down, b/c renin incr. NaCl and BP

MD CELLS ALSO MONITOR O2

• secrete erythropoietin in response to low O2

• allows for proliferation and helps mature RBCs to incr oxygen delivery

Renin

an enzyme that primarily acts a hormone (in the RAAS system specifically)

Renin triggers the Renin-angiotensin-aldosterone system (RAAS), which increases BP and adjusts diameter of the arterioles to maintain a stable glomerular filtration rate (GFR)

Secreted by JG cells

RAAS (system)

Renin triggers the formation of angiotensin II and aldosterone, which increase NaCl and water reabsorption in the proximal tubules and collecting ducts to raise blood pressure.

Renin also increases BP by changing diameter of ducts

Glycoprotein cover

Traps water in the ascending limb of the loop of Henle and the early DCT

ADH

Antidiuretic Hormone

Made by the SON (supraoptic nucluei in the posterior pituitary gland)

Leaves through the posterior lobe (one of two main lobes of the pituitary gland)

Allows Kidneys to Reabsorb water (back to blood)

Directly opens aquaporins (water channels) in the kidneys to reabsorb pure water (Doesn’t rely on salt to move the water)

helps to prevent dehydration

carried to the tubules of the nephron by the PT capillaries

Aldosterone

tells kidneys to reabsorb sodium (salt) back to the blood, with water following behind (osmosis)

ALSO secretes K+ (back to nephron)

Sodium leaves the urine and goes back to the blood at the expense of K+, which is secreted into to the urine

ALDOSTERONE IS STIMULATED BY LOW BP, LOW NA+, AND HIGH K+ (IN THE BLOOD)

High Na = High Osmolality

idk why this one’s blank

why’d you flip it over, it’s blank

Excretion

= Filtrate - reabsorption + secretion

= (Whatever was filtered - what was absorbed + what was secreted)

Glomerular filtration

Movement of large qty of water and solutes from the glomeruli into bowman’s space

ex. ions (Na+, K+, Cl-), nitrogenous waste (urea, uric acid, creatinine), and organic molecules (glucose, AAs)

Glomerular filtration is a passive process, that is dependent on Hydrostatic blood pressure (the force exerted by blood against the vessel walls, generate by heart’s pumping actions)

Qty in L of the amount of liquid that passes from plasma into the filtrate

180 L

protein too large to pass through to filtrate, too much protein in urine can be sign of greater issue

Glomerular capilaries

First layer of the filtration barrier

• has fenestrations

  • endothelial cells that carry negative charges

Basement Membrane

Second layer of the filtration barrier

• Meshwork of collagen and proteoglycan that has large spaces

• strong negative electrical charge

• The primary barrier to filtration

Podocytes

Third layer of the filtration membrane

• has negative charges

• hinders the passages of proteins (large molecules that are negatively charged in the kidneys, which helps repel from negative charge of the filtration barrier layers)

Things that are not filtered…

…Are not excreted through urination because they cannot pass through to the tubules of the nephrons

Things that cannot be filtered include:

• large charged molecules (ex. proteins)

Filtered (no secretion or absorption)

On track to becoming urine

ex. Inulin (an indigestible prebiotic fiber derived from plants like chicory root, used to boost digestion)

inulin is useful in measuring GFR

P_HB

Glomerular (blood) hydrostatic pressure

blood moving into the glomerulus

55 mmHg

P_O

Blood Colloid Osmotic Pressure

Pressure pushing against the glomerulus from Bowman’s space

30 mmHg

P_HC

Capsular Hydrostatic Pressure

Pressure pushing against the glomerulus near the tubule, which pushes with P_O

15 mmHg

Net pressure out of the glomerulus into the tubules (Net Filtration Pressure)

NFP = P_Hb - (P_O + P_Hc)

55 - 30 - 15 = Net 10 mmHg

PCT Reabsorption

Proximal Convoluted Tubule

Na/K pump on the basal membrane sets up gradient

• low na inside the cell

• lots of things here use na cotransport (ex. glucose, AAs, proteins)

water follows the solutes across the membranes in between the cells (osmosis; passive)

Filtered, Partial reabsorption (in PCT)

Most electrolytes are partially reabsorbed

Na+, Cl-, HCO3-

Filtered, complete reabsorption (in PCT)

Most nutritional substances

• ex. AAs, glucose)

Hyperglycemia

glucose >200 mg/dL (prolly don’t need to know this part)

BUT, carrier protein for glucose protein becomes saturated, leading to excretion of glucose

diuretic effect (polyuria, b/c incr. vol. of water; more water follows glucose)

polyuria —(leads to)—> polydipsia (dehydration) —> polyphagia (hungry)

Glucose movement (PCT)

Apical (luminal membrane); cotransport with Na+

Basal (BV side); Facilitated diffusion (down concentration gradient)

Na+ movement (PCT)

REABSORBED!

Apical; Cotransport with other molecules

Basal; Na/K ATPase, creates concentration gradient

• uses ATP (then becomes ADP)

K+ movement (PCT)

REABSORBED!!

Apical: Cotransport w/ Na+

Basal: Facilitated diffusion (high to low conc.)

Cl- movement (PCT)

REABSORBED!!

Apical: Cotransport w/ Cl-

Basal: cotransport w/ Na+

AA movement (PCT)

Amino acids

VERY IMPORTANT!! NEEDS TO BE REABSORBED!!

Apical: Cotransport w/ Na+

Basal: Facilitated diffusion

Water (PCT)

Water follows the osmotic gradient created by reabsorption of solutes (primarily sodium)

~65% reabsorbed

What supplies blood to cortical nephrons?

Peritubular capillaries

What supplies blood to Juxtamedullary nephrons?

both the PT capillaries and vasa recta

vasa recta supplies the loop of Henle that reaches deeper into the inner medulla

highly porous

acts to cycle salt

sluggish blood flow here (receives 10% of renal blood flow, 90% of blood flow is in the cortex)

Flow of blood in the vasa recta near loop of Henle

Ascending limb of vasa recta runs parallel to the descending limb of the loop of Henle

interstitial fluid runs in between

vice versa

water moves out of the descending limb of the loop of Henle, through the interstitial fluid and into the ascending vasa recta by osmosis

water does not move in the interstitial fluid between the ascending limb (loop of Henle) and descending vasa recta due to the glycoprotein cover on the ascending limb

Flow of filtrate in the loop of Henle

Filtrate moves down in descending limb of the loop of Henle, and up in the ascending

Descending limb of the loop of Henle

Filtrate moves down

permeable to water (water can leave to Interstitial fluid, then vasa recta)

passive?

Ascending limb of the loop of Henle

Thin then thick segment of the loop of Henle

Glycoprotein cover; traps water inside the tubule, but solutes can diffuse through to the vasa recta

What can leave the ascending limb of the loop of Henle?

Na, K, Cl, H2O

NKCC pump; on apical membrane

• uses sodium’s energy to move into the cell

• one sodium, needs one K and 2 cl- in order to work

• Na/K-ATPase on basal membrane creates gradient

  • na/k pump costs energy (ATP—>ADP)

Cl and K leaves the cells through facilitated diffusion (down their gradients)

Water cannot leave the tubule cells due to glycoprotein cover

Hydrogen Secretion

Secreted into PCT (see Renal 3 slide 26) by antiport mechanism (Na reabsorbed while H+ secreted; apical membrane)

comes into the cell from blood then leaves into tubule

Same in DCT

secreted in both PCT and DCT

Potassium Secretion

secreted in DCT

comes into tubule cell through antiporter with Na

leaves through tubule cell through antiporter with Na

see renal 3 slide 27

Movement of CO2 in PCT

comes from blood into the cell, cell has carbonic anhydrase inside, catalyzes reaction between CO2 and water, dissociates into H+ and HCO3- (bicarb)

When further away from the fast moving blood vessels of the fast moving blood vessels in the cortex ______________.

the slower things get back to the blood

salts don’t build up in cortex because of the fast moving blood vessels, so salt content here is similar to blood

Concentration gradient of the medulla

salts build up in the bottom of the medulla

salts don’t build up in cortex because of the fast moving blood vessels, so salt content there is similar to blood

Which part of the tubule system of the nephron has the highest salt content?

The space where the descending and ascending limb of the loop of Henle meet (1200 mOsm)

What amount of water is reabsorbed in the PCT?

65%

What leaves the descending limb of the loop of Henle? And where does it go? What is it impermeable to?

Water! (Passive transport)

Into the interstitial space then into the ascending vasa recta

Impermeable to salt!!

Is the filtrate in the descending limb of the loop of Henle Hypertonic or Hypotonic?

Hypertonic

Filtrate in the descending limb becomes salty (concentrated?)

BC WATER IS LEAVING

What leaves in the Ascending limb of the loop of Henle? Where does it go? What cant pass through?

NaCl leaves the thin segment (beginning) of the ascending limb of the loop of Henle through Passive transport

NaCl leaves the thick portion of the ascending limb leaves through active transport.

The salts leave into the interstitial fluid, unlikely to be picked up by vasa recta due to high salt concentration already

(Water is trapped due to the glycoprotein cover!)

Is the filtrate in the Ascending limb of the loop of Henle Hypertonic or Hypotonic?

Hypotonic

filtrate in the tubule becomes very dilute

BC SOLUTES ARE BEING REABSORBED!!

Blood moves ____ in the Cortex (HINT: speed)

Fast

When drinking water is not available, the kidney can produce a _____ volume of super concentrated urine. (HINT: quantity)

small

What happens when you drink a large amount of water?

Diluted urine

blood osmolarity drops

ADH levels decreased lower than normal, decreases amount of aquaporins

NaCl can leave the collecting duct to prevent large loss of electrolytes

Can cause temporary increase in BP

RAAS mechanism

Renin-Angiotensin-Aldosterone Mechanism

1. Kidneys detect decreased BP, results in incr. renin secretion (from JG cells)

2. Renin converts Angiotensinogen (protein from liver) to angiotensin I

3. Angiotensin-converting enzyme in the lungs convert angiotensin I to angiotensin II

4. Angiotensin II is a potent vasoconstrictor, results in incr. BP

5. Angiotensin II stimulates the adrenal cortex to secrete aldosterone

ANH

Atrial Natriuretic Hormone

produced by heart when BP incr.

inhibits release of ADH (incrs water reabsorption), Aldosterone (promotes retention of sodium and water, incr K secretion) and Renin (stimulates RAAS system, which incrs. water and salt retention)

Promotes Na and water excretion by the kidney (reduces kidneys’ ability to concentrate urine)

Results in decreased BV (blood vol) —> decreased BP

basically does the opposite of ADH, aldosterone, and renin (‘s downstream effects)

The concentration of the renal interstitial fluid is:

A. constant throughout the kidney

B. the greatest in the cortex

C. The greatest in the outer medulla

D. The greatest in the inner medulla

D. The greatest in the inner medulla

Renal blood flow is ___:

A. Constant throughout the kidney

B. the greatest in the cortex

C. The greatest in the outer medulla

D. The greatest in in inner medulla

B.

(inner medulla has sluggish blood flow)

Blood flow around the nephron (cortical nephron in this example, should be similarish to Juxtamedullary nephrons)

Blood comes inside through the arcuate artery → afferent arteriole → glomerulus → efferent arteriole —(then PT capillaries)→ down parallel to the ascending limb of the loop of Henle —(becomes blue here)→ then upwards parallel to the descending limb of the loop of Henle → arcuate vein

GFR equation

GFR = [P_Hb - (P_o+P_Hc)] x Fc

PURPOSE: GFR must remain constant over a range of dif. BPs

GFR = Glomerular filtration rate

• the total volume of fluid filtered from the glomerular capillaries into Bowman’s capsule per unit of time

P_Hb = Hydrostatic Pressure of Blood

P_O = Osmotic Pressure

P_Hc = Hydrostatic pressure of capsule

F_c = Filtration coefficient

P_Hb

Hydrostatic Pressure of Blood

• the push force from the blood pressure within the glomerular capillaries that drives fluid into the kidney’s filters

P_O

Osmotic Pressure

• The pull force exerted by proteins (like albumin) in the blood that tries to keep fluid inside the capillaries

P_Hc

Hydrostatic pressure of capsule

• The back-pressure from fluid already inside Bowman’s capsule that opposes further filtration

F_c

Filtration Coefficient

• A constant that represents the permeability and surface area of the filtration membrane

capillary permeability multiplied by surface area

_______ sometimes block fenestrations in the filtration barrier, which can affect filtration.

Antibodies

If qty of nephrons decrease, total surface area ________. What does that affect?

decreases

affects Fc

How do small changes in GFR affect salt and water excretion?

large changes in salt and water secretion

Intra-renal control of GFR

1. Myogenic control; vascular smooth muscle to respond to pressure changes

2. Tubuloglomerular controls; MD (Macula Densa Cells)

3. Prostaglandins; Can act locally to allow for vasodilation of the smooth muscle that makes up the blood cell. Provide short, small effect. Stimulated by body stress such as dehydration, stress(surgery, anesthesia, angiotensin II, sympathetic)

Myogenic Control of GFR

Tubuloglomerular feedback

High systemic pressure (response by Myogenic control of GFR)

146ml/min urine produced if BP is 140 mmHg

kidney responds by constricting afferent arterial (incr. resistance, flow in of blood), GFR returns to normal 125 mL/min

Once back to BP of 120 mmHg —> dilation of afferent arteriole

Normal Systemic pressure

120 mmHg (BP)

125 mL/min (GFR)

Low systemic pressure (response by myogenic control of GFR)

if bp = 100 mmHg (very low), GFR = 104 ml/min (waste product build up)

kidney responds by dilating the afferent arteriole to increase blood flow —> GFR to 125 ml/min,

once BP back at 120 mmHg, kidney responds by constricting afferent arteriole (decr. blood flow)

What produces renin? (HINT: Cell Type)

JG cells (juxtaglomerular cells) (endocrine cell)

Adenosine tells JG cells to ______ Renin production

Decrease

should lead to decreased retention of water b/c decr. RAAS stimulation

Less aldosterone = _____ sodium reabsorption

A. more

B. less

B. less

What happens when LOW NA+ is detected by the MD cells

Macula Densa cells

less adenosine released (by MD cells)(decreased vasoconstriction, so vasodilation) → allows for more filtration, more things flow into bowman’s capsule

less adenosine also means JG cells incr. renin production

→ which then increases amount of sodium reabsorbed

less adenosine →

adenosine = ATP??

JG cells are found ______________ (no nathan it is not the kidneys)(i mean technically yes but that’s not what the question is asking)

within the wall of the afferent arteriole near the glomerulus and renal corpuscle, forming the JGA (Juxtaglomerular apparatus)

Diuretic

Increases urine volume

Natriuretic

increases renal sodium excretion

Aquaretic

increases excretion of solute-free water

promotes water excretion without electrolyte loss

If mannitol is found in the PCT, water ____

water remains with mannitol, leading to less water reabsorption in the PCT

summary: water is normally reabsorbed in the descending limb, but can be trapped in the presence of mannitol

Mannitol is not commonly used therapeutically

• can be taken orally but not absorbed well in the GI tract

• causes incr. diarrhea

• better if given IV

How much water per day is reabsorbed from PCT through solute reabsorption?

FYI SLIDE

108 L/day

NHE3

Sodium Hydrogen ion antiporter (apical membrane)

Na from lumen to inside cell, H from inside cell to lumen

H ions come from the blood

(there is also a Na/K-ATPase on the basal membrane that sets up the gradient)

SGLT2

Sodium Glucose transporter found on the apical membrane

Carbonic Anhydrase (in the PCT)

Can be found on the apical membrane and inside the cell

CA inhibitor

Carbonic anhydrase inhibitor

traps sodium and bicarbonate in lumen

not k sparing

meaning this is a diuretic

ex. acetazolamide is a CA inhib.

Less HCO3 reabsorbed and less H+ secreted leaves the blood _______ (HINT: Think about blood pH)

Acidosis

Endogenous Anions

Anything you want to dump from the blood to urine to be excreted

here’s the pic if u want idk