2/3- glomerular filtration + clearance

kidneys lie behind what in the body

peritoneum

kidneys receive __% of cardiac output

20%

one nephron consists of what 2 structure

a glomerulus + a tubule

T/F: nephrons cannot pick out what we need to pee out

true, instead they selectively reabsorb tubule fluid or secrete solutes into it

renal corpuscle consists of which 3 structures

1. glomerulus

2. Bowman’s space

3. Bowman’s capsule

what are the 4 components of the glomerular filtration barrier between glomerular capillary lumen + Bowman’s space

1. glycocalyx of endothelial cells

2. endothelial cells

3. glomerular basement membrane

4. epithelial podocytes

glomerular basement membranes are usually ____ charged

negatively, allowing it to repel negatively charged important proteins away from the filtration site

clearance of a solute means

filtering that solute out of the blood and secreted out through urine

how do you calculate renal clearance aka glomerular filtration rate (GFR)

• Ux = concentration of solute in urine

• V = urine volume

• Px = concentration of solute in plasma

what’s the normal GFR of 2 kidneys

125 mL/min or 180 L/day

low GFR levels would cause

excretion of toxic material would be delayed

what is used to measure GFR

measuring creatinine (more practical) or inulin

why creatinine used to measure GFR

creatinine is not reabsorbed at all, therefore creatinine amount is the same before and after filtration

rising creatinine levels in one’s blood indicates

kidney failure

creatinine + GFR are _____ related

inversely

creatinine is not reliable in which type of pts

pts w/ decreased muscle bulk (ex: elderly, amputees, individuals affected by muscular dystrophy)

2 characteristics that determine a solute’s susceptibility to filtration

1. charge: + charged are more readily filtered, neutral charged <2 nm radius are filtered, - charged are not filtered

2. shape: rigid/globular molecules have low clearance

4 starling forces (pressures) present in the renal corpuscle that affect ultrafiltration

1. P_GC = glomerular capillary hydrostatic pressure

2. π_BS = Bowman’s space oncotic pressure

3. P_BS = Bowman’s space hydrostatic pressure

4. π_GC = glomerular capillary oncotic pressure

which starling forces pressures favor vs. oppose filtration

• favor: P_GC + π_BS

• oppose: P_BS + π_GC

Bowman’s space oncotic pressure (π_BS ) should always be

0, because there should be no proteins in the Bowman’s space

how do you calculate net filtration pressure (P_UF)

P_UF (mL/min) = (P_GC - P_BS) - (π_GC - π_BS )

how do you calculate renal plasma flow (RPF)

RPF = (1-Hct) x RBF

• Hct = hematocrit

this graph indicates what

low glomerular plasma flow

this graph indicates what

high glomerular plasma flow → increased GFR

what does filtration fraction (FF) measure

FF = GFR/RPF

high FF means what

low RPF, because GFR saturates at high values of RPF

3 essential functions of kidneys

1. remove metabolic products + toxins from blood → excrete them through urine

2. regulate body’s fluids, electrolyte balance, acid-base balance

3. produce/activate hormones involved in erythrogenesis, Ca²⁺ metabolism, regulation of BP

describe the pressure change as blood comes into through the renal artery

afferent arteriole sharply decreases pressure → pressure remains constant in glomerular capillary → efferent arteriole sharply decreases pressure → pressure decreases slightly in peritubular capillary

what controls the pressure in the glomerular capillary (P_GC)

constriction/relaxation of afferent + efferent arterioles

what happens when the afferent constricts while efferent relaxes

P_GC decreases

what happens when the afferent relaxes while efferent constricts

P_GC increases

what happens when only afferent constricts

P_GC + RPF decrease → GFR decreases

what happens when only efferent constricts

P_GC increases + RPF decreases + GFR increases then decreases

how do you maintain normal kidney function after losing a kidney

afferent arteriole resistance decreases → GFR in remaining kidney nearly doubles

angiotension II inhibitors effect afferent or efferent arterioles

efferent → decreases BP + GFR

what is used to measure renal plasma flow (RPF)

clearance of p-aminohippurate (PAH)

why is PAH used to measure RPF

kidneys almost completely clear the blood of PAH in a single pass + secreted in urine

which mechanism keeps renal blood flow + GFR constant

autoregulation, which has 2 mechanisms:

1. myogenic response

2. tubuloglomerular feedback (TGF)

what’s myogenic response

afferent arterioles have the ability to respond to changes in vessel circumference by contracting/relaxing via stretch-activated cation channels in vascular smooth muscle

what’s tubuloglomerular feedback (TGF)

via juxtaglomerulus apparatus:

macula densa cells sense an increase in GFR → contraction of afferent arteriole → P_GC + RPF decrease→ GFR decrease

whats the relationship between tubuloglomerular feedback (TGF) sensitivity + GFR

they have an inverse relationship

what 3 things decrease tubuloglomerular feedback (TGF) sensitivity

1. volume expansion

2. atrial natriuretic peptide (ANP)

3. high protein diet

4 systems that modulate renal blood flow + GFR

1. renin-angiotension-aldosterone axis

2. sympathetic nervous system

3. arginine vasopressin (AVP) aka antidiuretic hormone (ADH)

4. atrial natriuretic peptide (ANP)

renin-angiotensin-aldosterone axis’s role in modulating renal blood flow + GFR

• renin: catalyzes angiotensinogen → ang I, produced/stored in juxtaglomerular apparatus

• angiotensin: substrate of renin, produced by liver

• aldosterone: increases Na⁺ reabsorption rate, stimulated by ang II

lack of aldosterone leads to what

adrenal insufficiency (Addison disease): severe Na⁺ depletion, contraction of the ECF volume, + circulatory insufficiency

sympathetic nervous system’s role in modulating renal blood flow + GFR

increases both afferent + efferent resistance → decreasing RBF + GFR, RBF falling more than GFR due to preferential efferent constriction

AVP/ADH’s role in modulating renal blood flow + GFR

• increases water reabsorption in collecting duct by inserting aquaporin channels into tubular cells + increases vascular resistance

• decreases blood flow to renal medulla, minimizing washout of hypertonic medulla, which is essential for forming a concentrated urine

3 non-osmotic stimuli that increase AVP/ADH secretion

1. large blood loss

2. pregnancy

3. pain, nausea, drugs (morphine, nicotine, barbituates)

3 non-osmotic stimuli that decrease AVP/ADH secretion

1. volume expansion

2. alcohol

3. opiate-antagonist drugs

A

ANP’s role in modulating renal blood flow + GFR

• vasodilates afferent + efferent arterioles, increasing cortical + medullary blood flow

• lowers sensitivity of TGF mechanism to increase RPF + GFR

4 other vasoactive agents that modulate RBF + GFR

1. dopamine: vasodilates

2. prostaglandins: prevents excessive vasoconstriction

3. nitric oxide: vasodilates

4. leukotrienes: vasoconstricts