Chapter 18: Renal System - Powerpoint

what are the functions of the kidney?

* **extracellular fluid volume** (plasma and cardio function)
* **maintenance of fluid osmolarity** (\~300 mOsm)
* **maintenance of ion balance** (Na+, Ca+, and K+)
* **regulation of pH** (manipulation of H+ and HCO3-)
* **excretion of wastes** (nitrogen, creatinine, hormones, drugs, toxins)
* **hormone/cytokine and enzyme production** (erythropoietin, renin, vitamin D)

overview of urine formation

* amount excreted = amount filtered - amount absorbed + amount secreted
* E = F - R + S

how much is removed from the body per day?

* \~1.5L/day
* 50-1200 mOsm (dilute vs concentrated)

what are the three components off urine formation?

1. glomerular filtration (F)
2. tubular reabsorption (R)
3. tubular secretion (S)

what is glomerular filtration (F)?

* occurs in the renal corpuscle
* removal from blood to make filtrate: \~300 mOsm in plasma
* filtration fraction: \~20%

what is filtration fraction?

amount of plasma entering the glomerulus that is filtered out

what is tubular reabsportion?

* occurs in the proximal tubule, nephron loop, distal convoluted tubules and collecting ducts
* removing material, putting back into blood

what is tubular secretion?

* occurs in the proximal and distal convoluted tubule and collecting ducts
* putting back into filtrate (being made into urine)

when there is glomerular filtration, but NO reabsorption or tubular secretion, what occurs?

excretion = filtration

when there is glomerular filtration AND tubular secretion, but NO reabsorption, what occurs?

excretion is greater than filtration

when there is glomerular filtration AND some tubular reabsorption, but NO secretion, what occurs?

excretion is less than filtration

when there is a glomerular filtration AND total tubular reabsorption, but NO secretion, what occurs?

excretion is ____________ ??

what is the net filtration pressure in the glomerulus?

NFP = P_G - π_G - P_F

\
P_G = glomerular blood hydrostatic pressure (\~55 mm Hg) **OUT**

P_F = capsular hydrostatic pressure (CHP; \~15 mm Hg) **IN**

π_G = glomerular blood colloid osmotic pressure (BCOP; \~30 mm Hg) **IN**

what is glomerular filtration rate (GFR)?

how much you filter has a big impact on how much you excrete

what is inulin and how can it be measured?

polysaccharide not normally found in the body that is filtered but not reabsorbed or secreted

* **mGFR = (U_IN * V) / P_IN**
* U_IN = urine concentration of inulin
* V = urine volume per unit of time
* P_IN = plasma concentration of inulin
* can be used to monitor glomerular filtration rates by giving inulin intravenously to maintain P_IN
* **~7.5 L/hr or 125 mL/min**

how can creatine be a viable alternative to monitoring glomerular filtration rates?

* estimated GFR (eGFR)
* there is a constant production and constant plasma concentration but only a small amount is secreted, so GFR will be a little bit higher

what is renal clearance?

* clearance of solute (S) = mass excreted per time / plasma \[S\]
* volume off plasma from which S is removed per unit of time indicates how well you are removing something
* C_S = (U_S \* V) / P_S
* C_S = clearance of S
* U_S = urine concentration of S
* V = urine volume per unit of time
* P_S = plasma concentration of S

how do common drugs affect renal cleaance?

* impacts dosage and timing
* **aspirin > GFR**: filtering a lot more than normal, so aspirin is reabsorbed
* **warfarin** **< GFR**: does not get filtered because it is too large and hydrophobic
* **glucose < GFR = 0**: fully filtered, but will not get excreted because it gets reabsorbed

what is the relationship between age and GFR?

eGFR decreases with age (without kidney disease)

what is the relationship between GFR and kidney disease?

* 60-120 mL/min is considered acceptable ‘normal’
* < 15 mL/min requires dialysis (kidneys are not doing their job)

what are the stages of chronic kidney disease (CKD)?

* **stage 1**: possible kidney damage with normal kidney function
* eGFR and kidney function (%) = 90 or above
* **stage 2**: kidney damage with mild loss of kidney function
* eGFR and kidney function (%) = 60-89
* **stage 3a**: mild to moderate loss of kidney function
* eGFR and kidney function (%) = 45-59
* **stage 3b**: moderate to severe loss of kidney function
* eGFR and kidney function (%) = 30-44
* **stage 4**: severe loss of kidney function
* eGFR and kidney function (%) = 15-29
* **stage 5**: kidney failure
* eGFR and kidney function (%) = less than 15

what are two influencing factors that affect glomerular filtration?

1. net filtration pressure (NFP)
2. filtration coefficient

what is net filtration pressure (NFP)?

* majority of regulation
* increase in NFP = increase GFR
* kidneys will maintain GFR and renal blood flow (RBF) with MAP variability (90-180 mm Hg)
* constant filtration = constant pressure

true/false: NFP is dependent upon glomerular hydrostatic pressure (P_G)

true

what happens to net filtration in the afferent arteriole?

* direct relationship
* increase blood flow into glomerulus (vasodilate) = increase NFP and GFR
* decrease blood flow into glomerulus (vasoconstrict = decrease NFP and GFR

what happens to net filtration in the efferent arteriole?

* indirect relationship
* decrease blood flow out of glomerulus = increase GFR
* its harder or blood to drain away, so pressure builds up
* increase blood flow out of glomerulus = decrease GFR
* its easier for blood to drain away, so no pressure builds up

to decrease GFR:

\
vasoconstrict afferent = ____ resistance = ____ flow = ____ P_G = ____ GFR

increase; decrease; decrease; decrease

to decrease GFR:

\
vasodilate afferent = ____ resistance = ____ flow = ____ P_G = ____ GFR

decrease; increase; decrease; decrease

to increase GFR:

\
vasoconstrict afferent = ____ resistance = ____ flow = ____ P_G = ____ GFR

increase; decrease; increase; increase

to increase GFR

\
vasodilate afferent = ____ resistance = ____ flow = ____ P_G = ____ GFR

decrease; increase; increase; increase

how is net filtration pressure in the glomerulus regulated?

* local and autoregulation
* tubuloglomerular feedback mechanism
* myogenic response of afferent arterial
* neural control

how is the tubuloglomerular feedback mechanism involved in net filtration pressure in the glomerulus?

* kidney relies on self rather than nervous system
* macula densa detects Na+ in filtrate as a measure of GFR
* **increase Na+ in filtration** = increase Na+ in transport into cells = increase in osmotic gradient for water absorption = increase paracrine release = afferent arteriole vasoconstriction = **decrease GFR**
* decrease GFR = increase Na+ tubular reabsorption = decrease Na+ in transport into macula densa

the tubuloglomerular feedback mechansim is what kind of feedback loop?

negative

how is the myogenic response of afferent arterial involved in net filtration pressure in the glomerulus?

* **increase blood flow** = increase smooth muscle stretch = increase Ca2+ influx = increase smooth muscle contraction with afferent arteriole vasoconstriction = **decrease GFR**
* **decrease blood flow** = decrease smooth muscle stretch = decrease Ca2+ influx = decrease smooth muscle contraction with afferent arteriole vasodilation = **increase GFR**

how is neural control involved in net filtration pressure in the glomerulus?

* sympathetic system
* NE, E, and alpha-adrenergic receptors
* smooth muscle contraction = afferent arteriole vasoconstriction = decrease GFR

how does surface tension affect glomerular filtration?

glomerulus surface area: variable with action off messangial cells (fills in the space between capillaries and glomerulus)

how does permeability of the filtration membrane affect glomerular filtration?

* \~7 nm maximum
* size barrier: cellular components of blood, proteins, chemicals bound to protein
* permability of the substance

what hormones are involved in glomerular filtration?

* angiotensin II
* endothelin
* prostaglandins
* nitric oxide
* atrial natriuretic peptide (ANP)

what is angiotensin II?

* intermediate hormone in the renal pathway
* **vasoconstriction** = decrease GFR
* decrease filtration coefficient = decrease GFR

what is endothelin?

* comes from endothelial cells
* **vasoconstriction** = decrease GFR
* decrease filtration coefficient = decrease GFR

what is prostaglandins?

* effective in hemorrhaging
* vasodilation of both afferent and efferent arterioles will maintain blood flow to the kidney without changing GFR

what is nitric acid?

* vasodilation of both afferent and efferent arterioles will increase blood flow to the kidney without changing GFR
* bradykinins (associated with injury) stimulate the release of NO and prostaglandin

what is atrial natriuretic peptide (ANP)?

* vasodilation of afferent and vasoconstriction of efferent arteriole will increase GFR
* increase filtration coefficient will increase GFR

what is the basic function of the nephron?

remove, then resorb

why does the nephron filter so much, so fast?

we filter out a lot more than we need to, but then reabsorb the good stuff to get back to homeostasis

how much does the nephron filter?

* 70 kg person = 180 L/day
* glomerular filtration = \~300 mOsm (isosmotic)

how much does the nephron excrete?

* 70 kg person = 1.5 L/day minimum
* urine: 50-1200 mOsm (hyposmotic to hyerosmotic)

where does the most reabsorption occur?

proximal tubule reabsorbs water and solutes

what is transport maximum (Tmax)?

* we max out how much we can transport/move
* it is the saturation of the transporter resulting in excretion of the solute

what are two factors that influence Tmax?

1. **saturation of transporters**


1. # of solutes vs # of transporters and speed of transport
2. **renal threshold**


1. increase \[solute\] = no further increase in transport and reabsorption → solute excreted

what is the transport maximum for glucose?

* **filtration**
* filtered load = GFR x plasam \[glucose
* **increase** plasma \[glucose\] = **increase** GFR of glucose
* **reabsorption**
* max rate of glucose reabsorption: 375 mg/mL
* **when below Tmax**: increase \[glucose\] = increase reabsorption rate
* **when above Tmax**: increase \[glucose\] = decrease reabsorption rate
* **excretion**
* renal threshold is the plasma \[glucose\] first excreted
* **below threshold**: increase \[glucose\] = increase excretion
* **above threshold**: increase \[glucose\] = decrease excretion

what is glucosuria?

when glucose is in the urine

* increase plasma \[glucose\] = diabetes mellitus
* faulty glucose transporters = genetic

what does filtered load mean?

originally in plasma that was filtered out, is relative to plasma \[glucose\] and GFR

can there be a Tmax for active secretion?

if you have transport proteins, you can max out

what does reabsorption mean?

putting back into blood, is relative to Tmax

what is excretion?

relative to renal threshold, when you cannot absorb anymore, everything is excreted

what are the mechanisms for reabsorption?

1. passive processes
2. active processes
3. solvent drag

what is the passive process for reabsorption?

* solutes follow their electrochemical gradients
* net filtration favors water reabsorption
* aquaporin 1 (AQP1) channels for water reabsorption creates gradients for passive solute movement

what is active transport for reabsorption?

* **primary active transport**: Na+/K+ ATPase
* reabsorb Na+ to set up Na+ gradient
* **secondary active transport**: SGLT glucose symport with Na+ to get glucose back into the blood
* lumen to cell: apical cell surface
* **GLUT2**: glucose transporter follows concentration gradient
* cell to interstitial fluid: basolateral cell surface

what are other secondary active transports for reabsorption?

* **NKCC**: Na+/K+/2Cl- symporter in macula densa and ascending limb of loop
* **3 Na+/Ca2+ antiporte**r: returns Ca2+ to blood
* **Na+/H+ antiporter**: excretion of acids
* **Na+/HCO3- symporter**: reabsorption of base

what is solvent drag (bulk flow) in terms of reabsorption?

* paracellular reabsorption of water and solutes move with water
* solutes follow concentration gradient
* water and solutes move together

what is the osmolarity of the nephhrone tubules

* **proximal**: 300 mOsm
* **descending limb** = 300-1200 mOsm
* **ascending limb** = 1200-100 mOsm
* **distal** = 100 mOsm
* **collecting ducts (cortical and medullary)** = variable

what is the countercurrent multiplier system?

flow of filtrate vs flow of blood going in opposite directions; can adjust filtrate osmolarity to our needs


1. produces a hypertonic medullary interstitium
2. alters the osmolarity of the urine relative to the plasma and intersitium

what is a hyposmotic filtrate?

osmolarity of filtrate s less than the osmolarity of the plasma

what is a isosmotic filtrate?

osmolarity of filtrate is equal to the osmolarity of the plasma

what is a hyperosmotic filtrate?

osmolarity of filtrate is greater than the osmolarity of the plasma

* you have to excrete some water from kidneys

what happens in the loop of henle in the countercurrent multiplier system?

contains juxtamedullary nephrons

* thin descending limb is **permeable to water** (AQP1)
* 300 → 1200 mOsm
* thick ascending limb is **permeable to solutes** via active transport (Na+, K+, Cl-, HCO3-
* 1200 → 100 mOsm
* thin ascending limb has passive Na+ reabsorption
* 1200 → 100 mOsm

what happens in the vasa recta of the countercurrent multiplier system?

* blood flows in the opposite direction of the filtrate
* 300 → 1200 mOsm
* if air and blood equilibrated right away, you would get much less exchange
* 1200 → 300 mOsm
* water coming from descending limb comes back to vasa recta

what is urea handling?

maintains concentration gradients for water reabsorption

* filtered
* manipulated throughout
* maintains osmotic gradient through cortex and medulla

what happens in the distal convoluted tubule and collecting ducts during reabsorption?

* **principle cells**: water regulation
* **antidieuretic hormone / vasopressin** increases water reabsorption
* **aldosterone** increases Na+, Cl- and water reabsorption
* **atrial natriuretic hormone (ANP)** decreases water reabsorption
* **intercalated cells**: acid-base balance
* HCO3- and H+ handling

what happens during secretion?

* addition of solutes too filtrate: most occurs in PCT with additional secretion in DCT
* organic anion (OAT) and cation (OCT) transporters
* seccetion of drugs and medications
* secretion of some vitamins

what are electrolytes?

ions and small charged molecules

what are nonelectrolytes?

non-charged solutes

what are the key electrolytes?

H+ and HCO3- determine pH (acidemia and alkalemia)

what is HPO4^2-?

involved in pH balence

what is the role of Na+?

drives water balance, excitatory cell membrane potentials via secondary active transport

* hypernatremia vs hyponatremia

what is hypernatremia?

more sodium

* plasma osmoarity is increased
* water is going to leave and cause the cell to shrink

what is hyponatremia?

less sodium

* plasma osmolarity id decreased
* water is going into the cell and it will swell

what is the role of K+?

neuron function, excitatory cell membrane potentials

* hypokalemia vs hyperkalemia

what is hypokalemia?

less potassium

* resting membrane potentials become more negative
* becomes easier to activate cell, but harder to repolarize

what is hyperkalemia?

more potassium

* resting membrane potentials become less negative
* harder to activate the cell

what is the role of Ca2+?

neuron function, muscle function, hemostasis

* hypocalcemia vs hypercalcemia

what is hypocalcemia?

less calcium

* resting membrane potential becomes more negative
* harder to activate cell

what is hypercalcemia?

more calcium

* resting membrane becomes less negative
* easier to activate cell, but harder to repolarize

water follows solutes

\
**increase** ECF \[solutes\] = _______ ECF osmolarity

**decrease** ECF \[solutes\] = _______ ECF osmolarity

increase; decrease

true/false: change in cell volume can impact cell function

true

* **cells shrink** = dehydration headaches, confusion, unconsciousness
* **cells swell** = increase volume and pressure in cranium which restrict blood flow and oxygen to brain cells

some cells can maintain cell volume by adjusting their ____________

ICF \[solutes\] - the nephron tubule cells in hyperosmotic medulla

some cells use changes in cell volume as a signal such as the __________

liver

* swell = increase glycogen production
* shrink = increase glycogenolysis

how does the renal system regulate blood pressure?

endocrine and neuroendocrine control produces a slower and longer response compared to the heart

how does the cardiovascular system fix blood volume and pressure?

change cardiac output = change in blood pressure

how does the renal system fix blood volume and pressure?

whatever we do with Na+, we do with water

how does the hypothalamus regulate blood pressure?

monitors thirst

what is mass balance of water?

water intake = water excretion

* **intake**: drinking, food, metabolism of food
* **excretion**: urine, feces, sweat, exhalation, skin evaporation
* **regulated water loss**: what we can control (urine, sweat, feces
* **insensible water loss**: what we cannot control (exhalation, skin evaporation)

how is the kidney plasma volume reguated?

* normal: 180 L filtered/day
* 1.8 L excreted/day
* 99% reabsorbed

what is diuresis?

* production of hyposmotic urine
* getting rid of water because there is doo much of it in the plasma causing high blood pressure

how is hyperosmotic urine produced?

* water is reabsorbed and conserved

how is water involved in blood pressure regulation?

H2O excreted = H2O filtered - H2O absorbed


1. glomerular filtration
2. tubular reabsorption
3. modification of H2O reabsorption

what happens during glomerular filtration when water is involved in blood pressure regulation?

water can increase or decrease GFR and modify blood pressure of glomerular capillary with local control

* increase in P_G = increase in GFR (NFP) = increase H2O excretion
* decrease in P_G = decrease in GFR (NFP) = decrease H3O excretion

how is water balance regulated?

* with **local control** via the tubuloglomerular feedback and myogenic process
* with **neural and hormonal control** via baroreceptors that monitor pressure

increase plasma volume = __________ blood pressure

increase

* sympathetic system controls carotid arteries, aorta, Ig veins
* atria: atrial natriuretic peptide (ANP) involved in vasoconstriction and dilation