Ii. Renal Physiology 2

Front 1

Forces governing glomerular filtration rate (GFR)

Back 1

Favoring Filtration:
(1) arterial pressure (afferent capillary pressure)

Opposing Filtration:
(2) Bowman's capsule back pressure (increased by ureteral blockage)
(3) Plasma oncotic pressure (increased by dehydration)

Front 2

Proximal Convoluted Tubule (PCT), brief overview :

Back 2

(1) Receives glomerular filtrate which is isotonic to blood plasma (equal solute concentration & osmotic pressure, similar composition but lacks cells and large proteins)
(2) Cells reabsorb 66% of sodium along with water
(3) Filtrate passed on to Loop of Henle.

Front 3

Filtered load

Back 3

The quantity of any substance filtered per unit time. --> The plasma concentration of a substance filtered per minute

For Example; the filtered load of glucose (aka plasma glucose concentration filtered at the glomerulus) is directly proportional to the plasma glucose concentration. It also increases with diabetes. If the filtered load of glucose exceeds the level of absorption, will begin to excrete glucose.

Front 4

Descending vs. Ascending Loop of Henle

Back 4

Selective permeability in the two limbs.

ASCENDING: Thicker region, bigger cells, thicker walls, increased metabolism. Active pumping Na, KCl out from tubule fluid to medullary ECF --> acts to draw H2O out from DESCENDING loop of Henle. Osmolarity reaching tip is quite high as filtrate in the ascending limb becomes progressively hypotonic due to Na efflux. (Main purpose: is to generate a high osmotic pressure in the ECF surrounding the collecting duct, so water can be reabsorbed from CD.)

DESCENDING: Leaky to water but Na impermeable.

Front 5

Distal Collecting Tubule (DCT)

Back 5

Located in outer cortex. Turns and becomes the collecting duct towards medulla.

DCT provides selectivity of reabsorption (of Na, K, H , and Ca) in response to hormone effects.

Site of action for (a) Parathyroid hormone (PTH), (b) Calcitonin, and (c) Aldosterone.

(After 66% reabsorbed PCT, & 25% reabsorbed LOH,) Reabsorption of remaining 8 - 10% of filtered Ca is regulated by PTH and calcitonin at DCT.

Front 6

Parathyroid Hormone (PTH) Effects

Back 6

PTH site of action: DCT

Fxn: (1) Ensures maximum Ca absorption, and (2) blocks phosphate reabsorption in PCT

Front 7

Calcitonin Effects

Back 7

Calcitonin site of action: DCT

Fxn: Blocks effects of PCT; leading to decrease of Ca absorption and an increase in phosphate reabsorption

Front 8

Aldosterone Effects

Back 8

Fxn: Aldosterone controls reabsorption of remaining 8 - 10% of Na, in exchange for secretion of K or H into late DCT.

Little control for previous Na reabsorption, 90% is reabsorbed automatically (66% Na reabsorbed PCT, & 25% reabsorbed LOH). Remaining 9% is under selective reabsorption at DCT by aldosterone.

Front 9

Absence of Aldosterone...

Back 9

In absence of aldosterone, sodium excretion in the urine is quite high

Front 10

Sodium reabsorption in DCT...

Back 10

If sodium is reabsorbed in DCT (by aldosterone), its presence in ECF causes reabsorption of H2O.

Sodium is reabsorbed at DCT in exchange for secretion of K+ or H+ into the late DCT.

A combination of sodium reabsorption and K wastage (which occurs at 1:1 ratio) = bulks up circulatory volume (as water follows Na reabsorption)

Front 11

Levels of K secretion...

Back 11

Amount of K+ secreted by DCT is variable and reflects (1) dietary intake, (2) losses in case of diarrhea & vomiting.

LOW K+ SECRETION: (a) When tubular Na is low, as there is a 1:1 excretion. (b) When H+ secretion is more important (acidosis). (c) If the K+ gradient decreases during low K+ diet or due to K+ loss (diarrhea), tubular K+ secretion decreases to minimum.

HIGH K+ SECRETION: If body K+ rises, K+ may substitute for H+ in Na+ exchange. The K+ electrochemical gradient from tubule cell to filtrate increases, thereby increasing K+ secretion.

Front 12

Stimulus for Aldosterone Secretion

Back 12

Renin & angiotensin

Front 13

Juxtaglomerular Apparatus (JGA)

Back 13

Made up of 3 cell types:
(1) Cells of afferent arteriole (entering glomerulus)
(2) DCT cells
(3) Cells of Bowman's Capsule

An important collection of cells that work together to regulate renal responses to altered BP and body fluid composition or volume.

Front 14

JGA nervous input

Back 14

There is an important SYMPATHETIC NS input, which can provide one of the various stimuli that results in RENIN secretion from the JGA

Front 15

Renin Secretion

Back 15

Various stimuli such as (a) decreased renal arterial BP, or (b) increased sympathetic tone, results in secretion of the enzyme RENIN from the arteriolar granular cells of the JGA

Renin secretion leads to... (1) increased levels of angiotensin & aldosterone, (2) which both alter renal Na/K handling (and are therefore involved in body fluid balance).

Front 16

Renin-Angiotensin-Aldosterone System

Back 16

(1) Decreased renal arterial BP or increased sympathetic tone leads to secretion of renin from arteriolar granular cells of JGA.
(2) Renin leads to conversion of blood angiotensinogen to angiotensin I.
(3) Angiotensin I is converted in the lungs to active angiotensin II.
(4) Angiotensin II is (i) vasoactive, (ii) stimulates aldosterone secretion (stimulating Na reabsorption by DCT), and (iii) stimulates thirst and ADH secretion.
--> These affects all help restore BP.

(5) Renin secretion is eventually decreased by negative feedback.

Front 17

Aldosterone Effects

Back 17

(1) Sodium reabsorption in DCT, and further reabsorption of H2O
(2) Sodium : Potassium exchange (at gut & salivary glands) will conserve sodium
(3) Stimulates thirst
(4) Leads to increased sympathetic tone, which helps prevent stimulus of decreased BP
(5) Helps correct Na deficiency in ECF; restoration of Na:K ratio.

Front 18

Collecting Duct

Back 18

Whats left of filtrate after DCT comes down Collecting Duct (CD) --> passes through medulla interstitium.

The late section of the CT is under control of posterior pituitary hormone, ADH, which sets urine osmolarity.

In presence of ADH; Cells of CD made permeable to water. Filtrate = made hypertonic from the actions of the Loop of Henle (osmotic gradient created) which pulls H2O into ECF, down its concentration gradient

Absence of ADH; urine is hypotonic, a situation of water diuresis. The last 10% or so of H2O is open to excretion.

Front 19

ADH Release

Back 19

If ECF is hypertonic (relative water loss from plasma), ADH is released --> which acts on the channels of the collecting duct membrane, making H2O able to exit to inter-medullary interstitium.

In presence of ADH, can get 99%+ H2O reabsorption (vs. last 10% or so of water is open to excretion w/out ADH)

Front 20

Peritubular Capillaries Structure

Back 20

Blood vessel leaving glomerulus (efferent glomerular vessel) passes down/networks over the PCT, forms PERITUBULAR CAPILLARIES, before forming a loop (vasa recta) that dips down into the medulla paralleling the Loop of Henle, before returning to the cortex in association w/ the DCT --> eventually drains into renal vein.

Front 21

Peritubular Capillaries Fxn.

Back 21

Water is reabsorbed from PCT, taken up by peritubular capillaries. Plasma in peritubular capillaries is concentrated fm water loss by filtration; plasma w/ increased oncotic pressure is all ready for reabsorption.

Front 22

Peritubular Capillary Blood

Back 22

Peritubular capillary blood originates fm the glomerular capillary after filtration, when much water is lost, so oncotic pressure becomes higher. When this blood perfuses the peritubular capillaries, water reabsorption from the PCT is enhanced.

Front 23

Vasa Recta

Back 23

Formed from peritubular capillaries, dipping down alongside Loops of Henle. Important role is to maintain osmotic (sodium) gradient along bend of Loop of Henle.

Front 24

Peritubular Capillaries, Autoregulation.

Back 24

Peritubular capillaries help in an autoregulatory sense.

If drink lots of water; (a) glomerular pressure is higher, filtration rate is higher, (b) plasma dilution in peritubular capillaries means the oncotic pressure in peritubular vessels is lower (less likely to reabsorb water from PCT), (c) more aqueous fluid passes through to the medulla, (d) ADH inhibited under these circumstances leading to no reabsorption fm collecting duct either, (e) more urine formed --> an increased filtration rate, less water reabsorption at peritubular capillary & more fluid passing through PCT

This is an important element of renal water regulation known as GLOMERULO-TUBULAR BALANCE, which is an important AUTOREGULATORY MECHANISM; controlled by controlling blood flow to the glomerulus, which affects GFR.

Front 25

Increased GFR

Back 25

Increased GFR; less water reabsorbed fm PCT (lower oncotic pressure in peritubular capillaries), less water reabsorbed fm CD, increased urine volume

Front 26

Autoregulatory Mechanisms

Back 26

(1) Renal bloodflow, (2) glomerular filtration, and (3) tubular reabsorption are renal activities that can be controlled to regulate body fluid volume and composition.

These factors (bloodflow, GFR, and tubular reabsorption) are controlled by (A) Extrinsic, and (B) Intrinsic mechanisms.

Front 27

Intrinsic Autoregulatory Properties of Kidney

Back 27

(1) Effects on afferent end of renal capillary (altering afferent arteriolar muscle tone); (a) constriction to increase filtration rate, or (b) dilation to decrease GFR. --> Altering blood vessel diameter can maintain a constant GFR despite variations in BP.

(2) Glomerulotubular Balance; Involves changes in water recovery from PCT depending on ECF volume, GFR, and plasma protein concentration. (a) High ECF volume (from drinking lots of water, or thirst following Na intake) leads to increase in BP and GFR, reduced plasma protein concentration, low water reabsorption from PCT, and high tubular and urine flow rate. (b) Low ECF volume (dehydration) causes decreased GFR, high plasma protein concentration, increased water recovery form PCT, and decreased urine flow rate.

(3) Tubuloglomerular Feedback; Filtrate flow rate in DCT acts on macula densa cells of JGA to control GFR.

Front 28

Extrinsic Autoregulatory Properties of Kidney

Back 28

(1) Alternative inputs acting on aldosterone,
(2) Alterations in sympathetic NS input (increasing renin and aldosterone)
(3) Vasoactive factors; peripheral vasoconstriction acting to help restore BP at glomerulus.

Front 29

Diuresis

Back 29

Increased excretion of urine

Front 30

Glucose related diuresis

Back 30

Glucose handling in PCT; if glucose (osmotic particles) left in filtrate, can cause OSMOTIC DIURESIS, where less water is reabsorbed/more water is excreted in urine

Front 31

Drug induced diuresis

Back 31

Diuresis can be induced by drugs that act on regulatory sites in the nephron.

3 main target sites 4 diuretic drugs (used to increase rate of water passing through kidney, perhaps to remove excess fluid to decrease BP);
(1) PCT; which is a major site of water reabsorption. Carbonic anhydrase inhibitors decrease reabsorption of Na.
(2) Loop of Henle; most potent diuretics are called 'loop diuretics' which blocks cells in ascending loop of Henle to block Na, K, Cl reabsorption, inactivating the mechanism to form osmotic gradient to reabsorb water from collecting duct --> remaining water lost as urine
(3) DCT; preventing water reabsorption (by inhibiting sodium reabsorption)

Front 32

Body Water & Water Compartments

Back 32

60% body weight = water

2/3 body water = intracellular fluid (ICF)
1/3 body water = extracellular fluid (ECF)

Front 33

ICF / ECF Characteristic Features

Back 33

ICF: Lots K (main solute), little Na
ECF: Lots Na (main solute), little K

Front 34

Subdivisions of ECF

Back 34

(1) Plasma (retained in circulatory system)
(2) Interstitial fluid (ISF) surrounding cells

Front 35

Body Water flow

Back 35

Body water = free to move b/w different compartments (ICF, ECF; Plasma & ISF)

Front 36

Cardiac Output to Kidneys

Back 36

Kidneys are located in contact w/ blood plasma, and have a huge share of cardiac output (CO).

1/5 of CO circulates through kidneys. Kidneys ideally located to regulate H2O/Na balance by making small adjustments to fluid passing through them.

Front 37

Osmoregulation

Back 37

Maintenance of correct sodium concentration in ECF (extracellular fluid)

Front 38

Hypothalamus, monitoring ECF

Back 38

Hypothalamus = acutely sensitive to Na concentration in ECF, & by mechanisms; (1) ADH secretion, and (2) thirst, is able to make rapid and delicate changes to ECF sodium concentration.

Front 39

Increased Sodium Intake (eating crisps)

Back 39

Increased Na intake = quickly leads to change in ECF osmolarity; (1) leads to thirst, and (2) ADH release, --> Which ultimately leads to increased ECF volume

Front 40

Kidney; Na regulation

Back 40

Ultimately kidney wants to regulate Na content in the body. Best way is to keep ECF constant. Given osmoregulation (maintaining correct Na levels in ECF) is so critical and mechanisms for Na homeostasis are so delicate, making changes to ECF to balance osmolarity --> is done by VOLUME MEASUREMENTS.

Once received info about volume, kidney will adjust volume by sodium excretion or conservation, thereby altering sodium & volume.

Front 41

Mechanisms at Kidney's disposal

Back 41

Mechanisms kidney can use to alter body water and composition;
(1) Glomerular filtration
(2) Tubular reabsorption

Front 42

Link b/w filtration rate & peritubular capillary absorption rate

Back 42

Increased water intake; increases BP, and acts through glomerular apparatus, increasing GFR. Plasma protein concentration is reduced (by dilution) meaning that peritubular capillary oncotic pressure is low. Osmotic recovery of water from PCT is reduced, leading to high tubular flow rate and loss of sodium and water.

Conversely, decreased ECF volume leads to decreased GFR, high plasma protein concentration, increased water recovery from PCT, and decreased urine flow rate.

Front 43

Extrinsic control mechanisms of kidneys; VOLUME RECEPTORS

Back 43

Volume Receptors; control kidneys ability to respond to blood volume messages --> so kidney can make proper adjustments in Na handling, which will lead to changes in H2O volume. Comprise extrinsic regulation.

(1) Vascular Receptors; 2 types...
(a) Low Pressure Volume Receptors, which respond to FILL. (cardiac atria, pulmonary, and vascular locations)
(b) High Pressure Volume Receptors, which respond to PRESSURE. (located carotid sinus, aortic arch, & JGA--wouldn't expect to find these in venous circulation where BP is low).

(2) Other receptors; not much known about them. Located CNS & Liver.

Front 44

Rules to kidney Na/H2O handling

Back 44

(1) If there is an increase in circulating blood volume; leads to increased Na & water excretion

(2) Drop in circulating blood volume; leads to a decrease in Na & water excretion

Front 45

Kidney Receptors, mechanisms

Back 45

BOTH (1) neural, and (2) hormonal mechanisms are at play to relay info from receptors --> to kidneys

Front 46

Extrinsic control mechanism: Renal Sympathetic Nerves

Back 46

Renal Sympathetic Nerves, if ACTIVATED, are going to JGA and lead to decrease Na excretion

Mechanism: (a) Decrease GFR, and (b) increase renin

Sites of action: (1) Angiotensin; acts on PCT & LOH, (2) Aldosterone; DCT & CD, (3) ADH; CD

Front 47

Cardiac Atria, Pressure Volume Receptors

Back 47

Pressure Volume Receptors in cardiac atria, respond primarily to higher volume (too much fill in blood vessels) --> if activated, leads to secretion of atrial natriuretic hormone (ANP), which (1) causes NA excretion, (2) additional effect = blocks ADH

Secretion of ANP = only employed if too high circulating volume. For example, if large amounts of Na ingested, body regulates by taking in lot of water. If body is carrying extra circulating volume, it is picked up in atria of heart.

Mechanism to achieve atrial uresis (to get rid of extra circulating volume); involves Na excretion by (1) blocking aldosterone. (W/out aldosterone, DCT not going to conserve last 10% of filtered Na, which will pass out collecting duct to urine = which is natriuresis.) (2) decreasing renin, or (3) inhibiting angiotensin effects on the cortex.