NPB101 Renal Physiology

NPB101 Hamada SQ2025

Where does urine in the human body come from?

The blood

What does the urinary system consist of?

1. pair of kidneys

2. pair of ureters

3. urinary bladder

4. urethra

Ureters

Transport urine from kidneys to bladder

Bladder

stores urine until voided from body

Urethra

carries urine from bladder to the outside of the body

Blood enters and exits the kidneys

• enters the kidneys via the renal artery (connected to the aorta)

• exits the kidneys via the renal vein (connected to the inferior vena cava)

Nephrons, what are they and what they consist of

• structural and functional units of the kidney (functional unit is the smallest unit capable of performing all of the tasks of an organ)

• Each kidney has over 1 million of these units

• Each nephron consists of a renal corpuscle, which contains the glomerulus (which is a tuft of capillaries) and a renal tubule

Bowman’s capsule

the tubule forms a cup shape around the glomerulus called the glomerular capsule. Filters glucose, urea, NaCl, but NOT blood cells or proteins

How is urine produced?

1. Glomerulus (glomerular capillaries)

2. Bowman’s space in Bowman’s capsule

3. Proximal convoluted tubule

4. Proximal straight tubule

5. descending limb of loop of Henle

6. Thin segment of ascending limb of loop of Henle

7. Distal convoluted tubule

8. cortical collecting duct

9. medullary collecting duct

10. renal pelvis

_% of the plasma that enters the glomerulus is not filtered and leaves through the efferent arteriole

80

_% of the plasma that enters the glomerulus is filtered

20

Approx __ liters of glomerular filtrate formed each (collectively)

180

Average plasma volume is ___ liters

2.75

The entire plasma volume is filtered by the kidneys about ___ times per day

65

Of the 180 liters of plasma filtered each day, ___ liters are reabsorbed

178.5

3 basic processes involved in the formation of urine

1. glomerular filtration (GF)

2. tubular reabsorption (TR)

3. tubular secretion (TS)

Glomerular filtration

non-discriminant filtration (except for red blood cells) of a protein-free plasma from the glomerulus into Bowman’s capsule (amount filtered)

Tubular reabsorption

selective movement of filtered substances from the tubular lumen into the peritubular capillaries (amount reabsorbed)

Tubular secretion

selective movement of non filtered substances from the peritubular capillaries into the tubular lumen (amount secreted)

Amount Excreted Equation

Amount excreted = Amount filtered - Amount reabsorbed + Amount secreted

2 Capillaries in Renal Physiology

• Glomerular

• Peritubular

Glomerular Capillary

• Specialized for filtration. These are the only capillaries in the body that are fed and drained by an arteriole (afferent and efferent)

• Allows the blood pressure in the capillary bed to be very high and forces fluid and solute out of the blood into the glomerular capsule

Peritubular capillaries

Most of the filtrate is reabsorbed in the renal tubule cells and returns to the blood through the peritubular capillaries

Each nephron consists of 2 components

1. Vascular component

2. Tubular component

Vascular components

• afferent arteriole

• Glomerulus

• Efferent arteriole

• Peritubular capillaries

Tubular component

• Bowmans capsule

• Proximal tubule

• Loop of Henle

• Distal tubule and collecting duct

What is a more efficient filter in the kidney ?

Glomeruli due to membrane having a large surface area and very permeable to water and solutes

What factors are NOT filtrated at the Bowman’s capsule?

• Protein

• Blood cells

• Glucose

• Urea

• NaCl

1. Protein

2. Blood Cells

Where does glucose go after its filtered at the bowman’s capsule

reabsorbed at proximal tubule

Where does urea go after its filtered at the bowman’s capsule

partially reabsorbed at proximal tunnel and collecting duct

Where does NaCl go after its filtered at the bowman’s capsule

reabsorbed at proximal tubule, loop of Henle and distal tubule

What do glomerular capillaries allow blood pressure in the capillary bed do?

Allows it to be very high and forces fluid and solute out of the blood into the glomerular capsule

What is a common finding when there is a problem with the filtration membrane?

Blood cells or protein in the urine (protinuria) which is common in diabetes and hypertension

3 forces involved in glomerular filtration

1. glomerular capillary blood pressure

2. plasma-colloid osmotic pressure

3. bowman’s capsule hydrostatic pressure

Glomerular capillary blood pressure

the fluid pressure within the glomerular capillaries.

• Favors filtration

Plasma-colloid osmotic pressure

caused by unequal distribution of protein btwn plasma (contains proteins) and glomerular filtrate (no protein). H₂O wants to move down osmotic gradient into glomerulus.

• Opposes filtration

Bowman’s capsule hydrostatic pressure

The fluid pressure by the filtrate in Bowman’s capsule.

• Opposes filtration

What is the major force that causes glomerular filtration?

Glomerular capillary blood pressure

What is the glomerular filtration rate (GFR)

Volume of filtrate formed each minute

What is GFR affected by?

The volume of surface available, filtration membrane permeability and net filtration (NFP), blood pressure/blood flow to the glomerular capillaries

What is GFR directly proportional to?

To the NFP (net filtration pressure). Increases in systemic blood pressure mean increases in GFR

If blood pressure is elevated, is the GFR high or low?

high, changes in GFR. result mainly from changes in glomerular capillary blood pressure

How can the kidney adjust blood flow to maintain stable filtration?

Adjust the size of afferent artieole

If GFR increases bc of a rise in arterial pressure, then…

reduces due to vasoconstriction (decreases blood flow into the glomerulus)

If GFR decreases bc of a fall in arterial pressure, then …

enlarge due to vasodilation (increases blood flow into the glomerulus)

what are the 2 mechanisms that keep GFR stable

1. autoregulation (intrinsic control)

2. sympathetic control (extrinsic control/uses nervous system)

Both work by changing caliber and resistance of afferent arterioles

Autoregulation of GFR

• helps maintain a constant blood flow into the glomerular capillaries

• done by changing the caliber of the afferent arterioles

2 mechanisms of GFR autoregulation

1. Myogenic mechanism

2. Tubuloglomerular feedback mechanism

Myogenic mechanism

a common property of vascular smooth muscle is to contract automatically in response to increased stretch and to relax in response to decreased stretch

tubuloglomerular feedback mechanism

allows the tubule of a nephron to monitor the rate of fluid movement and make adjustments to GFR to maintain appropriate flow

Juxtaglomerular apparatus

region near the glomerulus where the tubule passes through the fork formed by the afferent and efferent arterioles

Tubuloglomerular feedback mechanism

• involves the juxtaglomerular apparatus

• allows the tubule of a nephron to monitor the rate of fluid movement and make adjustments to GFR to maintain appropriate flow

juxtaglomerular (granular) cells

• enlarged smooth muscle cells that have secretory granules which contain the hormone renin

• mechanoreceptors (sense blood pressure) in the afferent arteriole

Macula densa cells

• group of tall, closely-packed cells that are adjacent to the granular JG cells

• chemoreceptors that respond to changes in the NaCl content of the filtrate

• detect changes in rate fluid is flowing and release

• local acting vasoactive chemical

Glomerular Filtration

autoregulation via juxtaglomerular apparatus

What is the primary purpose of renal autoregulation?

a. To increase urine output during physical activity

b. To maintain a stable glomerular filtration rate (GFR) despite flunctatavions in blood pressure

c. To temporarily halt kidney function during periods of stress

d. To enhance blood supply to the bladder

B. To maintain a stable glomerular filtration rate (GFR) despite fluctuations in blood pressure

When blood pressure increases, how does the kidney auto regulate to maintain a stable glomerular filtration (GFR)?

a. The afferent arteriole dilates to increase blood flow

b. The afferent arteriole constricts to decrease blood flow

c. The efferent arteriole constricts to increase glomerular pressure

d. The glomerulus collapses to stop filtration

B. The afferent arteriole constricts to decrease blood flow

Baroreceptor reflex function (GFR: Sympathetic Control)

• arterial carotid sinus and aortic arch baroreceptors detect rises and falls in arterial blood pressure

• Sends signals to cardiovascular control center in brainstem which then adjusts levels of sympathetic activity

• uses nervous system

Sympathetic control Baroreceptor reflex example

If the plasma volume decreases bc of hemorrhage

• baroreceptors detect drop in blood pressure

• cardiovascular control center coordinates an increase in sympathetic activity

• sympathetic activity not only increases cardiac output and total peripheral resistance but also decreases GFR (to maintain plasma volume by constricting afferent arterioles)

Transepithelial transport, how big and what do they contain

• Throughout its entire length, tubule is one cell-layer thick

• Tubular epithelial cells have a luminal membrane and a basolateral membrane. Adjacent tubular cells form tight junctions

• Interstitial fluid fills the gaps (lateral spaces) btwn epithelial cells.

• Except for water, materials must pass through the cells to leave tubular lumen and enter the blood

Extracellular fluid (ECF)

• 80% interstitial fluid

• 20% plasma

Five steps that requires a substance cross 5 barriers for trans-epithelial transport

1. The luminal membrane of the tubular cell

2. the cytosol of the tubular cell

3. the basolateral membrane of the tubular cell

4. the interstitial fluid

5. the capillary wall

Two type of tubular reabsorption

1. passive reabsorption

2. active reabsorption (requires energy)

Passive reabsorption

movement down an osmotic or electrochemical gradient

Active reabsorption (requires energy)

• active step in Na+ reabsorption involves the energy-dependent Na+/K+ ATPase carrier located in the tubular cell’s basolateral membrane

• includes glucose, amino acids, organic molecules, Na+ and other electrolytes

Na+ reabsorption

• The intracellular concentration of Na+ is low (bc of the Na+/K+ ATPase), Na+ diffuses into the tubular cell down its concentration gradient

• The interstitial concentration of Na+ is high (bc of the Na+/K+ ATPase), Na+ diffuses into the peritubular capillary down its conc. gradient

Where does reabsorption take place Na+?

Na+ reabsorption rate varies across the different location of the nephron; 99.5% of filtered Na+ is reabsorbed

Proximal tubule Na+ reabsorbed

67% of filtered Na+ is reabsorbed, regardless of the amount of Na+ in the body fluids

• reabsorption of glucose, amino acids, H2O, Cl- and urea

Loop of Henle Na+ reabsorbed

25% of filtered Na+ is reabsorbed, regardless of the amount of Na+ in the body fluids

• H2O urine of varying conc and volumes

distal and collecting tubules Na+ reabsorbed

8% of filtered Na+ is reabsorbed, Na+ reabsorption subject to hormonal control, being important in the regulation of ECF volume

Distal and collecting tubules Hormonal control: Na+ reabsorption

• aldosterone stimulates Na+ reabsorption

• Atrial natriuretic peptide inhibits Na+ reabsorption

How does aldosterone increase Na+ reabsorption

In distal and collecting tubules by promoting the insertion of Na+ channels (luminal membranes) and Na+/K+ ATPase carriers (basolateral membranes)

Angiotensinogen

synthesized in liver, always present in plasma

Renin

released from kidneys (granular cells) into plasma. Activates/converts angiotensinogen into angiotensin I

Angiotensin-converting enzyme (ACE)

enzyme present in the lungs that converts angiotensin I into angiotensin II

Angiotensin II

has many effects (stimulates vasopressin, thirst, arteriolar vasoconstriction). Also stimulates the adrenal cortex to release aldosterone

Renin-angiotensin-aldosterone system (RAAS)

Atrial Natriuretic peptide (ANP)

• Hormone that serves to increase the excretion of Na+ in the urine

• Specialized cardiac atrial cells produce and store ANP. ANP is released when they’re stretched due to expansion of the ECF volume

Actions of ANP: ___ Na+ reabsorption in the distal and collecting tubules

inhibit

Actions of ANP: ___ Renin secretion by the kidneys and aldosterone secretion from the adrenal cortex

inhibit

Actions of ANP: ___ smooth muscle of afferent arterioles (input to glomerulus). The leads to dilation of the afferent arterioles and an increase in the GFR

inhibit

Actions of ANP: ___ sympathetic nervous system, thereby decreasing cardiac output and total peripheral resistance

inhibit

Glucose and amino acids reabsorption

• glucose and amino acids are reabsorbed in the proximal tube

• Na+ is important role for the reabsorption

• kidneys usually conserve all the glucose and protect against loss of the important nutrient in the urine

Active Na+ reabsorption

responsible for the passive reabsorption of Cl-, H2O, and urea

Chloride Reabsorption

• Cl- ions are passively reabsorbed down the electrical gradient created by active reabsorption of Na+

• Cl ions pass btwn (not through) tubular cells

H2O Reabsorption

• occurs passively by osmosis throughout the length of the tubule

• 80% is obligatory reabsorbed in the proximal tubules and loops of Henle; variable amounts of the remaining 20% are reabsorbed in the distal portions of the tubule (under hormonal control- vasopressin)

• water channels “aquaporins” in the proximal tubule are always open; channels in the distal tubule are regulated by vasopressin

Urea Reabsorption

• Indirectly linked to active Na+ reabsorption

• Waste product from the breakdown of protein

• Osmotically induced reabsorption of H₂O in the proximal tubule secondary to active Na+ reabsorption produces a concentration gradient for urea that favors passive reabsorption of this waste

What happens to the cell’s equilibrium potential if the extracellular K+ concentration increases from 5 mM to 50 mM, while intracellular K+ remains at 150 mM?

Ek = -90mV (ECF: ICF = 5mM: 150mM)

1. The cell’s equilibrium potential is less polarized (less negative or closer to 0).

2. The cell’s equilibrium potential is more polarized (more negative or farther from 0).

3. Nothing changes

The cell’s equilibrium potential is less polarized (less negative or closer to 0)

What is tubular secretion an important mechanism for? (4)

1. disposing of drugs and drug metabolites

2. eliminating undesired substances or end products that have reabsorbed by passive processes (urea and uric acid)

3. removing excess K+

4. controlling blood pH

What are the most important substances secreted by the tubules in tubular secretion?

H+, K+, and organic anions, cations

Tubular Secretion: H+

• the ability of the kidneys to secrete H+ is important for the acid-base balance of the body

• extent of H+ secretion depends on the acidity of the body fluids (H+ con in the body fluids is too low → H+ secretion decreases)

• H+ can be secreted by the proximal, distal, and collecting tubules

Tubular Secretion: K+ ions (where is it absorbed and secreted)

actively reabsorbed in the proximal tubule and actively secreted in the distal and collecting tubules

Tubular Secretion: K+ reabsorption (proximal tubule)

constant and unregulated; almost all filtered K+ is reabsorbed

Tubular Secretion: K+ Secretion (distal and collecting tubule)

subject to regulation; almost all K+ in the urine is K+ that was secreted

What happens if K+ levels are low?

K+ secretion in the distal portion of the nephron is reduced to a minimum

What happens if K+ are high?

K+ secretion in the distal portion of the nephron is increased

Nerst equation

equation describing the equilibrium potential for a particular ion

If the cell’s resting potential is moved towards threshold (depolarized), then…

the cell would be over excitable

If the cell’s resting potential is moved away from threshold (hyper polarized), then …

the cell would be under excitable

What does the basolateral pump do in K+ secretion?

it simultaneously transports Na+ into the lateral space and K+ into the tubular cell