Glomerular Filtration

factors limiting glomerular filtration

1. as molecular weight of proteins increases, the filterability of them declines 2. negatively charged molecules are more restricted than neutral molecules, regardless of their size. This is opposite of positively charged molecules, which are restricted less.

Starling forces across the glomerular capillaries

1. at beginning of capillary, blood has just come from the afferent arteriole - no filtration has occurred so the net filtration pressure favors filtration 2. At the end of the capillary, the blood has been filtered. Protein is left behind so the osmotic pressure increases - eventually filtration halts as net filtration pressure approaches zero

Effects of afferent and efferent arteriolar vasoconstriction or vasodilation on glomerular capillary hydrostatic pressure (Pgc), the glomerular filtration rate (GFR), and renal blood flow (RBF)

1. if *afferent* arteriole *constricts*: glomerular hydrostatic pressure decreases, so GFR decreases, and RBF will also decrease 2. if *efferent* arteriole *constricts*: glomerular hydrostatic pressure increases, so GFR increases, but RBF will decrease 3. if *efferent* arteriole *dilates*: glomerular hydrostatic pressure decreases, so GFR decreases, but RBF will increase 4. if *afferent* arteriole *dilates*: glomerular hydrostatic pressure will increase, so GFR increases, and RBF will also increase essentially, glomerular hydrostatic pressure and GFR will always mirror each other, but RBF will always decrease with constriction and increase with dilation

CO in human and rest and GFR

20-25% of CO goes to kidney despite it's small mass 25% of the blood to the glomerulus gets filtered

factors inhibiting renal renin release

ADH renal hypertension increased Na or Cl concentration in distal tubular filtrate increased GFR ANP angiotensin II & aldosterone (negative feedback)

list the important paracrine factors that affect the kidney

Adenosine: vasoconstriction in kidney Prostaglandins: vasodilatory and counter SNS and angiotensin II effects NO: vasodilatory Endothelin: vasoconstrictor

Renal Circulation

Blood enters the nephron via the renal artery two arterioles and two capillary beds are involved glomerular capillaries filtrate plasma peritubular capillaries reabsorb a large percentage of filtrate and the secretions of certain substances into the filtrate

juxtaglomerular apparatus and the macula densa

Consists of: macula densa - senses changes in blood pressure juxtaglomerular cells (granular cells) of afferent arteriole make renin extraglomerular mesangial cells are also part of the complex, but have an unknown function

Glomerulus components

Endothelium Basement membrane Epithelium Pericytes (mesangial cells)

Starling Equation and GFR

GFR = Kf * (Pgc - Pbc - PIgc) Kf = filtration coefficient (represents permeability and surface area of the filtration barrier - more permeable to water and larger surface area, so higher Kf = more filtered from glomerular capillaries than other capillaries Pgc = hydrostatic pressure in glomerular capillaries Pbc = hydrostatic pressure in Bowman's capusle PIgc = plasma oncotic pressure in glomerular capillaries

how are RBF and GFR regulated?

autoregulation (small changes) - normal fluctions in blood pressure can be regulated by paracrine factors (tubuloglomerular feedback) ANS (short term) and hormones (long term) - result in larger changes in arterial blood pressure through SNS, renin-aldosterone-angiotensin system, or ANP/BNP

angiotensin II's effects on RBF and GFR

can constrict both efferent and afferent arterioles at low levels, ang.II preferentially constricts efferent arterioles - this decreases RBF but increases GFR at higher levels (hemorrhage), angiotensin II constricts both afferent and efferent arterioles to maintain GFR and RBF

GFR, hydrostatic, and protein osmotic (oncotic) pressures

capillary blood hydrostatic pressure favors filtration bowman's space interstitial fluid hydrostatic pressure opposes filtration capillary blood protein osmotic pressure opposes filtration there is no bowman's space protein osmotic pressure since there's little protein filtered

factors that affect GFR

changes in RBF changes in glomerular capillary hydrostatic pressure increased permeability of glomerular filter decrease in total area of glomerular capillary bed aging (GFR decreases) tubuloglomerular feedback changing in hydrostatic pressure in bowman's space changes in concentration of plasma proteins

autoregulation via afferent arterioles

changes via activation of stretch-sensitive calcium receptors (on macula densa?) - when they're activated, the smooth muscle on the afferent arteriole contracts filtration rate needs to be constant - if too low, it won't get rid of urea and creatinine, if too high then overwhelms capacity of tubular system to reabsorb water and solutes

cortical nephrons, juxtamedullary nephrons, and the vasa recta

cortical nephrons - don't go as deep juxtamedullary nephrons - important in concentrating urine for species that live in dry habitats peritubular capillaries entwine with or are close to the tubular system

ANP and BNP effects

counterregulatory mechanism of RAA system dilation of afferent arterioles but constriction of efferent arterioles dilation effect more pronounced, so increase in RBF = increase in GFR

tubuloglomerular feedback

if increase in BP or renal blood flow or GFR, that's going to cause more Na and Cl to the juxtaglomerular apparatus (macula densa cells) - they sense increased Na, H2O and Cl moving through the area, so the macula densa signal the release of vaso-activated substances which can cause vasoconstriction to the afferent arteriole

the major effects of increased renal SNS activity on juxtaglomerular granule cells, tubules, and arterial vessels

if increase renal SNS activity = fight or flight situation - other systems are more important right now, although both afferent and efferent arterioles have alpha-1 receptors 1. renin rate is increased 2. sodium excretion rate is decreased 3. renal blood flow and glomerular filtration rates are decreased, since alpha receptors are more prominant on the afferent arteriole, so vasoconstriction occurs there.

Myogenic autoregulation

increased RBF => increased stretch in arterial walls => the smooth muscle on the afferent arteriole contracts reflexively to decrease blood flow pressure diuresis is also described here, which is an increased urine output as a result of increased arterial BP

Q, R, and BP in the kidney

kidneys are unique in having two sites of regulation (arterioles) - *major mechanism for changing blood flow is by changing the arteriolar resistance or diameter* has a higher pressure than other capillary beds

glomerular filter compared to normal capillary bed

more leaky to ions, water, and small molecules while being less leaky to proteins if small proteins DO get filtered, most of them are reabsorbed in the proximal tubule via endocytosis

glomerular filter (importance of size and charge)

negative charges in the basement membrane due to heparan sulfate and glycoproteins in the epithelial cells prevent negatively charged proteins from wanting to get through, even if they are small enough to fit lipophilic compounds like steroid and thyroid hormone aren't filtered b/c bound to albumin or other transport proteins Ca2+ is also bound to proteins in the blood

filtration in glomerulus

occurs at afferent end higher overall pressures for afferent to efferent - because two high resistance arterioles, hydrostatic pressure stays fairly constant across the capillaries through the glomerulus oncotic pressure increases within capillary when get to efferent end because more fluid is being filtered through the capillary bed but the proteins remain

Endothelium of glomerulus

pores (fenestrae) that allow diffusion of solutes and some proteins, but not RBCs

proteinuria

protein in urine filtrate will look more like interstitial fluid than plasma there exist different kidney diseases where the glomerular filter breaks down - can lose the negative charges on various proteins int he filtration barrier, so smaller proteins show up in the urine

basement membrane of glomerulus

proteins, for the most part, cannot get through negatively charged due to heparan sulfate

factors stimulating renal renin release

renin release increased by: 1. drop in BP 2. reduced GFR 3. reduced concentrations of sodium and chloride in the tubules 4. SNS input to the kidneys 5. circulating catecholamines

mesangial cells (pericytes) of glomerulus

surround capillary endothelial cells and exhibit contractile characteristics similar to smooth muscle cells (reduce area available for filtration) phagocytic functions in removing trapped material from the basement membrane of capillaries

glomerular filtration rate

the volume of fluid filtered per minute from the glomerular capillaries into Bowman's space it's a product of net filtration pressure and the filtration coefficient

epithelium of glomerulus

these include the podocytes with foot processes that are negatively charged due to glycoproteins within between the foot processes are filtration slits podocytes possess long extensions that wrap around the capillaries and contact the outer part of the basal lamina