Physiology - Renal 1

Osmolarity formula

(pic from internet)

What is the effect of constriction/ dilation of afferent or efferent arteriole on GFR?

***** If afferent arteriole is squeezed, there will be lower flow and lower glomerular capillary hydrostatic pressure and therefore lower GFR - if afferent arteriole is dilated, flow into capillary will increase, hydrostatic pressure and GFR will increase But if Efferent arteriole is squeezed (constricted), there will be back pressure into capillary, there will be greater capillary hydrostatic pressure and higher GFR

What acts as signal to stimulate autoregulation?

***delivery of Na+ and Cl- acts as signal to stimulate autoregulation

What is the movement of H2O in terms of oncotic pressure?

- H2O moves from lower oncotic pressure to higher oncotic pressure

What are the determinants of Net Filtration Pressure?

*oncotic pressure of fluid in Bowman's capsule is very small because proteins are not filtered

What is is the osmolarity of solution containing 150mmol/L NaCl?

150mmol/L x 2 = 300 mOsm/L NaCl: dissociates in solution into 2 particles

What is the passageway of fluid from kidney to bladder?

Cortex -> Medulla -> Minor & Major calyces -> Renal pelvis (collection point) -> ureter -> bladder *there are 2 ureters, one for L and one for R kidney

What are the determinants of πgc?

Determinants of glomerular capillary oncotic pressure: - renal plasma flow (as flow↓ πgc↑)

Peritubular capillaries that surround loop of Henle are called

Vasa Recta (Vasa Recta lies parallel to Loop of Henle)

Juxtaglomerular cells are found in

afferent arteriole

Renal artery separates into

smaller arterioles -> afferent and -> smaller blood vessels which will further collect into renal vein

What is Macula densa?

specialized area of cells of thick ascending loop of Henle - detects changes in Na+, Cl- concentrations - main function is to regulate blood pressure and the filtration rate of the glomerulus.

Glomerulus

specialized tuft of capillaries

What happens in the kidneys if renal sympathetic nerve activity is increased?

↑activity of renal sympathetic nerves causes constriction of both afferent and efferent arterioles - as result Renal blood flow↓ by a lot (both afferent and efferent constricted), this will increase ability to concentrate proteins, so glomerular capillary oncotic pressure↑ - NFP and GFR will both ↓ - On the other hand, constricting both arterioles leads to small↑ in glomerular capillary hydrostatic pressure, which will oppose increase in oncotic pressure. End result there will be small decrease in NFP and GFR *But over time, glomerular capillary hydrostatic pressure will↓, flow through arterioles will reduce, GFR↓ and there will be larger↓ in NFP and GFR

Constricting afferent arteriole leads to .... GFR and ... RBF

↓GFR ↓RBF

The juxtaglomerular cells secrete renin in response to:

- Stimulation of the beta-1 adrenergic receptor - Decrease in renal perfusion pressure (detected directly by the granular cells) - Decrease in NaCl concentration at the macula densa, often due to an decrease in glomerular filtration rate (from wiki)

Number of viable nephrons is dictated by

- age (more nephrons die with age) - disease (DM = more nephrons die) less nephrons = less surface area = less Kf = less GFR

What is the autoregulatory range of RBF and GFR

- autoregulation of RBF or GFR doesn't involve nerves or hormones = tries to preserve GFR and RBF in the face of minute to minute changes in the blood pressure Autoregulation works at range Autoregulation doesn't work in hemorrhage because it's out of autoregulatory range It's there to preserve GFR and RBF in small changes in BP

NO is produced by ..... as response to ....

- endothelial cells - as response to increases in AngII or sympathetic nervous activity at afferent/efferent arterioles NO is labile gas with half-life = 6sec NO is produced by endothelial cells, it diffuses to smooth muscle where it activates soluble Gluanylyl Cyclase which then increases cGMP, which relaxes vascular smooth muscle

magnified cross-sectional juxtaglomerular complex

- it's a V where there's efferent arteriole (away from glomerulus) and afferent arteriole (to glomerulus) - macula densa demarcates difference between distal convoluted tubule and thick ascending limp of loop of Henle - note cells of macula densa touch cells of afferent arteriole (supply blood to kidney)

Juxtaglomerular apparatus consists 2 cell types:

- macula densa cells (part of distal convoluted tubule of the same nephron) -juxtaglomerular cells (also known as granular cells) = specialized smooth muscle cells of the afferent arteriole, which supplies blood to the glomerulus

What factors regulate GFR?

- nerves and hormones

Symbol of oncotic pressure is

- pi

What are the physical aspects that regulate filtration of substances?

- size of substance: the larger the ion/compound, the harder it is for it to go through glomerular capillary - electrical charge: -charged molecules are less filtered, because surfaces of filtration barrier are coated with -charge which repels -charged molecules form going through

What is the effect of AngiotensinII in renal artery stenosis?

- squeezes efferent more than afferent - tries to Preserve GFR as close to normal as possible in condition of lower renal blood flow (not increasing, just preserving GFR) In patients like that if you block Angiotensin II GFR will collapse and pt can die

What are the determinants of constriction/dilation of afferent or efferent arterioles?

- sympathetic nerves - Renin-angiotensin autoregulation - prostaglandins/ NO/ Dopamine (dilate)

What is the function of prostaglandins?

- vasodilator ** modulate any increase in sympathetic nervous activity or any increase in AngII that affect kidneys When AngII or sympathetic nerves constrict afferent and efferent arterioles, endothelial cells of arterioles produce prostaglandins; as result vessels don't get as constricted as they can be

What can increase in sympathetic nervous system activity?

- volume loss - hypotension => decrease stretch in baroreceptors causing decreased parasympathetic firing, increased sympathetic firing => GFR and filtration ↓ to prevent fluid loss

Renal blood flow is determined by

1 - MAP (mean arterial pressure) 2 - contractile state of renal arterioles

Fluid from Glomerular capillaries moves through

1 - endothelial cells of the capillaries (End cap) 2 - glomerular basement membrane (GBM) 3 - slit diaphragms between podocyte foot processes (marked E on pic)

What influences Kf?

1) Permeability on the kidney side is determined by: - size of fenestra between capillary endothelial cells - size of pores between epithelial podocytes of Bowman's capsule 2) Surface area: determined mesangial cells status + number of nephrons

Normal GFR is about

180 L/day 180L/ day x 1/24hr x 1/60min x 1000ml = 125ml/min * nephron is very active; it's filtering 125ml/min in a normal person. So there's a lot of reabsorption (going back into the blood otherwise you'll be peeing all day) As person gets older GFR decreases.

NFP example

A. pressure of -10 and -19 means that they are both acting against filtration (trying to keep fluid in glomerular capillary) +45 acting with filtration Overall NFP = 45 - 19 - 10 = 16 B. Shows NFP = 0 = means there's no filtration - doesn't happen in humans - happens in rats

What converts Angiotensin I -> Angiotensin II

ACE = angiotensin converting enzyme

Afferent arteriole vs Efferent arteriole

Afferent arteriole brings blood to the glomerulus and the Efferent arteriole takes blood away from the glomerulus. The efferent arterioles either: 1) carry blood to capillaries in the medulla (Vasa recta) or 2) form anastomotic capillaries in the cortex (peritubular plexus).

The first part of the nephron is ....

Bowman's capsule

Filtrate from glomerulus is collected into

Bowman's capsule - small molecules like Na, AA, glucose leak through fenestrations in endothelial layer of the capillaries - proteins can't get out because basement membrane prevents them leaking into Bowman's space

What are the 2 regions of kidney on a macroscopic level?

Cortex = outer region Medulla = inner

What are the determinants of Pgc?

Determinants of Glomerular hydrostatic pressure: - caliber of arterial pressure (if there's constriction/dilation of afferent or efferent arteriole)

What are the 2 processes of autoregulation of RBF and GFR

Don't worry about myogenic response Know tubuloglomerular feedback (TGF)

(Filtered Load + Secretion) - Reabsorption =

Excretion

Glomerulus is the main site for .....

Filtration

Movement of fluid from plasma to interstitial space through the capillary wall is called ....

Filtration

Movement of fluid from glomerular capillary -> Bowman's capsule -> proximal tubule is called

Filtration **amount filtered is called Filtered load

If glomerular surface area is increased because of relaxation of mesangial cells, Kf will ... and GFR will ...

Filtration rate increases GFR increases

Overall equation for GFR is

GFR = Kf x NFP

GFR formula

GFR = Kf x NFP (net filtration pressure) Kf = Permeability x Surface area = Ultrafiltration Constant

Is there change in GFR Over the Length of glomerular capillary?

GFR decreases As fluid is filtered into Bowman's capsule, capillary oncotic P increases, Net filtration pressure decreases and GFR↓ over the length of the glomerular capillary **whenever we're talking about GFR, we're talking about average

If systemic or plasma oncotic pressure go up, GFR will

GFR will go down - that means plasma proteins go up, oncotic pressure will go up, NFP will go up and GFR will decrease

Rate at which filtered load is filtered is called

Glomerular filtration rate

H2O moves from solution with ... osmolarity to solution with .... osmolarity

H2O moles from lower to higher osmolarity - because when you have higher osmolarity there's more osmotic pressure to pull solution from lower to higher osmolarity (high osmolarity attracts H2O)

If there's an obstruction of tubule or obstruction in ureter or urethra, what is the effect on GFR?

Hydrostatic pressure of Bowman's capsule doesn't change much under physiological conditions. But changes in diseases. - obstruction in tubule, ureter or urethra can increase back Pressure all the way up to kidney nephrons. Hydrostatic P (Pbc) in Bowman's will increase and NFP will decrease. As result GFR will decrease.

What is the effect of increased efferent arteriole resistance on GFR?

If efferent arteriole resistance is increased, that means arteriole is constricted. There will back pressure back into glomerular capillary and glomerular capillary hydrostatic pressure will increase. GFR will increase.

What is the effect of decreased renal plasma flow on GFR?

If renal plasma flow decreases, plasma has smaller volume, glomerular capillaries will have smaller volume per unit time. That means it'll be easier to concentrate proteins. Average glomerular oncotic pressure will go up and GFR will decrease When renal plasma flow goes down, not only does glomerular capillary hydrostatic pressure goes down, but glomerular oncotic pressure will go up. And therefore GFR will go down.

How does Tubuloglomerular feedback work

If there's increase in arterial BP (ex. during exercise, horror movie), glomerular capillary hydrostatic pressure will increase and GFR will increase. This will increase delivery of NaCl to macula densa (since with increased GFR there will be increased filtration). Macula densa is located close to afferent and efferent arterioles. Signal from macula densa is sent to afferent arteriole, which is most likely a signal Adenosine. In kidney Adenosine is a constrictor. Afferent arteriole will constrict in response to Adenosine. Glomerular capillary hydrostatic pressure will decrease. GFR is marinated in the face of changes in arterial pressure.

Explain what happens during hemorrhage (include arterial pressure, GFR, renin, AngII )

In hemorrhage there's ↓arterial pressure. Through baroreceptors, activity of renal sympathetic nerves increases, which directly stimulated granular cells through beta-adrenergic receptors to increase Renin secretion *renal nerves directly innervate granular cells Increased stimulation of renal sympathetic nerves decreases GFR Decreased GFR reduces fluid delivery to macula densa and this leads to ↑renin secretion ↓Arterial pressure decreases stretch of granular cells (intra-renal baroreceptors) and this leads to ↑renin secretion ↓Arterial pressure directly decreases GFR, which leads to reduced fluid to macula densa and ↑renin secretion ↑Renin secretion increases AngII ↑Ang II is a vasoconstrictor; it increases resistance and arterial pressure (know! on exam)

What are the determinants of GFR

Kf x NFP = Kf x (Pgc - Pbc - πgc)

What is regulated in the plasma compartment?

Na+ and H2O

Is albumin permeable under normal circumstances?

No

Does glomerular filtrate contain cells?

No - it's protein, cell free - contains most inorganic ions and low MW organic solutes (Na+, Cl-, phosphate, Mg++, Ca++)

Is net filtration pressure equal throughout the glomerular capillary?

No Hydrostatic P in Bowman's capsule is constant Hydrostatic P in glomerular capillary is relatively constant throughout the capillary Oncotic P of glomerular capillary isn't constant (it increases)

What is the difference between osmotic and oncotic pressure?

Osmotic P = takes into account ions in solution Oncotic P = only takes into account proteins in solution - solution with more proteins has higher oncotic pressure

2 major prostaglandins that are produced in endothelial cells of renal arterioles

PGI2 (prostacyclin) and PGE2

How are kidneys endocrine organ?

Produce hormone Renin and Erythropoietin Renin function: - involved in production of Angiotensin II (potent vasoconstrictor) - effect on kidney Erythropoietin function: - involved in increase of production of RBCs from bone marrow (don't need to know more)

Movement of fluid form nephron tubular lumen into peritubular capillary (blood vessel) is called

Reabsorption - movement from lumen into blood

What is the effect of constriction on renal blood flow if constriction happens in afferent or efferent arteriole?

Renal blood flow is different form GFR because with renal blood flow it doesn't matter where constriction/dilation happens (afferent or efferent arteriole) Whether constriction happens in afferent or efferent arteriole the end result is ↓Renal blood flow (it doesn't matter where increased resistance happens = same result ↓RBF) ***With GFR it does matter where constriction happens.

Movement of fluid from blood (peritubular capillary) back to nephron lumen is called ...

Secretion - blood to lumen

What is Kf?

Ultrafiltration coefficient

All fluid from nephron is collected into minor and major calyces and then into renal pelvis to form

Urine

Damage to the macula densa would impact blood flow to the kidneys because

afferent arterioles would not dilate in response to a decrease in filtrate osmolarity and pressure at the glomerulus would not be increased. As part of the body's blood pressure regulation, the macula densa monitors filtrate osmolarity; if BP drops, the macula densa causes the afferent arterioles of the kidney to dilate, thus increasing the pressure at the glomerulus and increasing the glomerular filtration rate. The macula densa does not regulate the dilation of the efferent arterioles and afferent arterioles do not dilate in response to increases in filtrate osmolarity. (wiki)

osmolarity vs fluid volume charts

at 0 mark = cell membrane (separation between ECF and ICF) solid line = normal dotted line = change From 0 fluid is increasing going L and going R A. ECF and ICF volumes increased, but osmolarity is decreased. This can be due to: movement of H2O into both compartments H2O goes into ECF compartment so V there ↑ and osmolarity↓. H2O goes into intracellular space. Osmolarity in ECF will then increase a little (still lower than original) and the equilibrium settles between two compartments. B. ECF volume and osmolarity ↑, ICF fluid volume ↓ but osmolarity ↑ Cause: injection of hyperosmotic (hypertonic) saline => this will increase both volume because injection is directly into plasma and osmolarity in ECF; this causes H2O movement from intracellular compartment to ECF and this causes ICF volume to lower while osmolarity of ICF increases. Overtime there will be osmolarity equilibrium between 2 compartments C. Both ICF and EDF volume ↓, osmolarity↑ Cause: Dehydration; loss of fluid D. Both ICF and ECF volume↑, osmolarity↓ Cause: injection of hypo osmotic saline

Why is Oncotic P of glomerular capillary isn't constant throughout?

because as you're moving along the capillary, fluid is being filtered into Bowman's capsule and that concentrates glomerular capillary oncotic pressure (it rises) Therefore Net filtration pressure decreases over the length of the glomerular capillary

What is renal blood flow?

blood that flows from Renal Artery traverses all nephrons then back into Renal Vein *it's not the same as GFR

Interstitial fluid and plasma are separated by

capillary wall (extracellular compartment)

Extracellular and intracellular compartments are separated by

cell membrane

Cortical collecting tubule

collecting duct, located in the cortex

Macula densa contributes to

control of glomerular filtration and secretion of renin from granular cells (juxtaglomerular cells)

Renin function

converts Angiotensinogen -> Angiotensin I

Is Glomerulus located in the cortex or the medulla of kidney?

cortex

Proximal convoluted tubule is located in the ... of kidney

cortex

In normal situation what is the effect of Angiotensin II on GFR?

decreased GFR - constricting efferent arteriole more than afferent tends to increase glomerular capillary hydrostatic pressure - since Angiotensin II is a powerful vasoconstrictor, it tends to reduce renal blood flow systemically and this can cause decrease in glomerular capillary hydrostatic pressure Decrease in renal blood flow increase glomerular capillary oncotic pressure Overall AngII decreases Kf by acting on mesangial cells (decreases filtration surface area through construction) Therefore overall Ang II reduces GFR (because decreases Kf)

How does decreased afferent arteriole resistance affect GFR?

decreased afferent arteriole resistance means arteriole dilates, there's ↑flow, ↑hydrostatic pressure in glomerular capillary and therefore ↑GFR

As molecular radius of the molecule increases, filtration ...

decreases *goes down after certain point *goes down even faster if the molecule is negatively charged *after certain point in radius filtration reduces for larger radius and -charge, however its reduced for -charged a lot more Alb = albumin

4 major functions of kidneys

don't worry about acid base balance for this class

Glomeruli capillaries give rise to ..

efferent arteriole

Peritubular capillaries are supplied by

efferent arteriole

Body fluid is found in ... compartments

extracellular (1/3) and intracellular (2/3 of total body water)

Filtered substances go through (in order):

fenestrae = latin for window

Extracellular means

fluid outside of all cells

Intracellular means

fluid within all cells

What are mesangial cells?

found in core or between efferent and afferent arterioles

Filtration is movement of fluid from ....

glomerular capillaries to bowman's capsule Each nephron begins in a renal corpuscle, which is composed of a glomerulus enclosed in a Bowman's capsule. Ultrafiltrate (has negligible plasma proteins) enters Bowman's space. **Filtration is driven by Starling forces. Ultrafiltrate is passed through: Proximal convoluted tubule -> loop of Henle -> distal convoluted tubule -> series of collecting ducts to form urine

GFR

glomerular filtration rate = volume of filtrate formed per unit time = rate at which glomerulus filters fluid into Bowman's capsule & proximal tubule

Oncotic pressure regulates fluid movement across ...

glomerulus and peritubular capillaries of kidneys

Juxtaglomerular cells are also called

granular cells

Greater osmolarity gives .... osmotic pressure

greater

Juxtaglomerular cells secrete

hormone Renin

How does RBF indirectly determine GFR?

if there's more renal blood flow, there will be higher renal hydrostatic pressure and therefore ↑GFR

What if both afferent and efferent arteriole are constricted?

if you squeeze both sides, initially glomerular capillary hydrostatic pressure will increase. Filtration rate will increase and there will be more fluid filtered out. But over time because afferent arteriole is constricted, GFR will decrease. So GFR goes up first and then goes down (it's like putting a pinhole in hose. So initially due to P there more fluid will flow out of pinhole. But with time there will be less pressure because a lot of fluid was pushed out)

Dopamine acts to ...

increase RBF and inhibit secretion of Renin

If there're more nephrons, surface area is

increased lower # nephrons = less surface area for filtration

Vasa recta gives rise to

interlobular veins, other veins then into renal vein

Renal blood flow is all the blood that flows

into the kidneys through renal arteries and the out of the kidneys through renal veins

What is juxtaglomerular complex?

juxtaglomerular apparatus is part of the kidney nephron, next to the glomerulus. It is found between afferent arteriole and the distal convoluted tubule of the same nephron (near vascular pole of glomerulus) This location is critical to its function in regulating renal blood flow (BP) and glomerular filtration rate. The juxtaglomerular apparatus is named because it is next to (juxta) the glomerulus. It consists of 3 types of cells: 1 - macula densa (ending of ascending limb of Loop of Henle) 2 - juxtaglomerular cells (also known as granular cells) => secrete renin 3- extraglomerular mesangial cells

Renin is produced by

juxtaglomerular cells (granular cells)

Signals from macular densa can quickly be detected by

juxtaglomerular cells of afferent arteriole to initiate production of renin

Oncotic pressure is important force in ...

kidneys

What are prostaglandins?

local metabolites of arachidonic acid

Osmolarity is measured in

mOsm/L

Demarcation point where thick ascending limb becomes distal convoluted tubule is ...

macula densa

Collecting tubule in medulla is called

medullary collecting tubule (know all the regions of kidney in order; on exam)

What is osmosis?

movement of water across cell membranes

The functional unit of kidney is called ...

nephron *there are 1million nephrons in each kidney *each nephron is highly segmented, and each segment is relatively specialized

Does Angiotensin II work on afferent or efferent arteriole?

on both, but has more effect on efferent

Driving force for the movement of H2O is the ...

osmotic pressure difference across cell membrane = driving force is the GRADIENT and the gradient is made by Osmotic Pressure differences across cell membrane

Efferent arterioles give rise to ...

peritubular capillaries

When kidneys regulate fluid volume, they are really regulating fluid volume in ....

plasma - but by regulating fluid in plasma (ECF), you can be also regulating fluid in the interstitial fluid. Ex. if plasma has high osmolarity, there will be net movement of fluid from interstitial space to plasma or there also can be exchange between ICF and ECF compartments But it always starts from ECF space

Extracellular compartment is further divided into

plasma (1/4) and interstitial compartment (3/4)

Angiotensin II is ...

powerful vasoconstrictor

Bowmans capsule continues into

proximal convoluted tubule

Dopamine is produced by ..

proximal tubule

Glomerular filtration rate

rate at which blood is filtered through glomerulus into Bowman's space Glomerular filtration is bulk flow (water and ions are flowing out of glomerular capillary into Bowman's capsule

Peritubular capillaries travel alongside nephrons and allow for ....

reabsorption and secretion between blood and the inner lumen of the nephron. Peritubular capillaries surround the proximal and distal tubules, as well as the loop of Henle, where they are known as vasa recta

In kidney prostaglandins production is stimulated by

renal sympathetic stimulation and Ang II - prostaglandins are produced by almost all nucleated cells

Controlling Angiotensin II is done through controlling ...

renin

Levels of Angiotensin II are dependent on levels of

renin **increased levels of renin will increase Angiotensin II

Slit diaphragms are regulated by

several proteins (don't memorize) - therefore regulate amount of fluid that can go through

The afferent arterioles later diverge into ...

the capillaries of the glomerulus

For the most part nephron traverses

the cortex and medulla of the kidney

The larger the fenestrae (window) ...

the easier fluid will go through endothelial cells of glomerular capillaries

The larger the slit diaphragm

the more likely the fluids can go through

Osmotic pressure is determined solely by ...

the number of solute particles in the solution

When mesangial cells are relaxed

they increase surface area = when contracted, decrease surface area of filtration

Thin descending limb continues into ....

thin ascending limb -> thick ascending limb **thick ascending loop goes back to very close proximity of glomeruli (efferent and afferent arteriole)

Proximal convoluted tubule gives rise to ..., which is located in ..... (cortex or medulla)

thin descending loop of Henle medulla

Peritubular capillaries function

tiny blood vessels, supplied by the efferent arterioles, that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron = surround kidney nephron

IS Dopamine a vasodilator or constrictor?

vasodilator

If there's increase in renal arterial pressure, there will be ..... in perfusion pressure in afferent arteriole, .... hydrostatic pressure in glomerular capillary and .... GFR

↑ in perfusion pressure in afferent arteriole ↑ hydrostatic pressure in glomerular capillary ↑GFR

Constricting efferent arteriole leads to .....GFR and ....RBF

↑GFR but ↓RBF