Module 4: Renal Physiology

Question 1

Concept of Water Balance

Answer 1

Intracellular Fluid (ICF):
- Fluid within the cells that comprise about two thirds of total body fluid.

Extracellular Fluid (ECF):
- Fluid around the cells, including the plasma, interstitial fluid, lymph and transcellular.

Question 2

ECF Volume and Osmolarity

Answer 2

Volume:
Regulated to maintain blood pressure. Maintenance of salt balance for long term regulation of ECF volume

Osmolarity:
Maintained to prevent swelling and shrinkage of cells

Question 3

Control of ECF Volume

Answer 3

Increase in ECF increases plasma volume, thereby increasing arterial blood pressure

Short term control Factors:
- Baroreceptor Reflex - mechanoreceptors in arteries which control cardiac output and total peripheral resistance to impact blood pressure
- Fluid Shift - Fluid can be shifted from interstitial compartments or plasma to compensate for the other

Long Term Control Factors:
- Fluid Input/Output - Control of urine output by the kidneys

Question 4

Control of Salt

Answer 4

When salt is transported across a membrane, so it water due to osmosis

Salt Input:
Maintain through diet. need 3.5g/day

Salt Output:
Excrete excess through feces, sweat and kidneys

Question 5

Hypotonicity

Answer 5

Hypotonicity of the ECF is associated with overhydration

Renal Failure:
- Not able to produce a concentrated urine

Rapid Water Ingestion:
- Kidneys can deal with the high volume in a timely manner

Over Secretion of Vasopressin:
- Vasopressin promotes water retention

Question 6

Hypertonicity

Answer 6

• Insufficient water intake, or not drinking enough
• Diabetes insipidus, which involves a deficiency in vasopressin
• Excessive water loss due to heavy sweating during extreme exercise, vomiting or diarrhea

Question 7

Regulation of Water Balance

Answer 7

1. Hypothalamic osmoreceptors monitor osmolarity of the fluid surrounding them
   - As osmolarity increases, vasopressin is secreted and thirst is stimulated
   - Not stimulated if hypotonic
2. Vasopressin increases water reabsorption at kidneys, while thirst stimulates water intake

• Atrial volume receptors can also activate hypothalamic pathways

Question 8

Kidneys Functions

Answer 8

1. Maintain water balance in the body
2. Maintain body fluid osmolarity
3. Maintain proper plasma volume
4. Help maintain acid-base balance
5. Regulate ECF solutes (such as sodium, potassium, chloride, calcium, phosphate, and others)
6. Excrete wastes of metabolism
7. Excrete foreign compounds ingested
8. Produce erythropoietin
9. Produce renin
10. Activate vitamin D

Question 9

Kidney Structure

Answer 9

Adrenal Gland on each kidney
- Renal cortex on the outside
- Renal medulla on the inside
- Inner core is renal pelvis which is channeled to the ureter

Question 10

The Nephron

Answer 10

Vascular Component:
Glomerulus - Capillary where water and solutes are filtered from
Renal Artery - delivers blood and divides into arterioles
Afferent Arterioles - supplies blood to nephron
Efferent Arterioles - Transport unfiltered blood from the glomerulus
Peritubular Capillaries - Subdivide from efferent arterioles and deliver oxygen to renal tissues

Tubular Component:
Bowman’s Capsule - Encircles glomerulus and collected filtered fluid
Proximal tubule - highly coiled
Loop of Henle - Dips into renal medulla
Juxtaglomerular Apparatus - ascending limp of Henle loop that is surrounded by afferent and efferent arteries
Distal Tubule
Collecting duct - travels deep into renal medulla
Renal pelvis - where nephron empties

Question 11

Types of Nephron

Answer 11

Cortical Nephrons:
- Loop of Henle only slightly dips into medulla and are small.
- 80% of all nephrons
- Primarily serve secretory and regulatory functions

Juxtamedullary Nephrons:
- Found on the inner layer of cortex and henle descends deeper into cortex
- Hairpin loops of vasculature called vasa recta that are close to loop of henle
- Responsible for concentration and dilution of urine

Question 12

Basic Renal Processes

Answer 12

Glomerular Filtration:
- 20% of blood in glomerular capillaries is filtered into Bowmans capsule
- Plasma does not normally contain protein but has the same solute concentrations

Tubular Reabsorption:
- Important substances returned to peritubular capillaries.
- 178.5 litres reabsorbed from 180 each day

Tubular Secretion:
- Selective transfer of substances from peritubular capillaries into tubules to filter remain 80% of plasma

Question 13

Glomerulus

Answer 13

• Network of capillaries that filter blood across walls into Bowman’s capsule
• Receives blood supply from afferent arterioles and exits into efferent arterioles

Glomerular Filtration Rate:
- Rate at which blood is filtered through all of the glomeruli

Question 14

Glomerular Filtration

Answer 14

Filtrate must pass three layers of glomerular membrane

1. Glomerular Capillary Wall - single layer of endothelia cells that contain large pores to increase (100X) permeability of fluids and solutes.
2. Basement Membrane - Layer of collagen and glycoproteins that repel filtration of small plasma proteins due to negative charge
3. Inner Layer of Bowman’s Capsule - Composed of podocytes that form narrow filtration slits for fluid tansfer

Question 15

Forces that Regulate Glomerular Filtration

Answer 15

Glomerular Capillary Blood Pressure:
- Afferent arteriole diameter is larger than efferent, to increase resistance of blood leaving the glomerulus.
- Higher pressure 55 mmHg

Plasma-Colloid Oncotic Pressure:
- Presence of large proteins that can’t be filtered produced oncotic force, that resists water movement into the Bowman’s capsule
Bowman’s Capsule Hydrostatic Pressure:
- Pressure of fluid in Bowman’s Capsule
- Resists movement of water out of the glomerular capillaries

Question 16

Glomerular Filtration Rate

Answer 16

Dependent on filtration pressure, surface area and membrane permeability

Glomerular Filtration Rate = Filtration Coefficient (Kf) x Filtration Pressure

Net Filtration Pressure = Glomerular Capillary Blood Pressure - (Plasma-colloid Oncotic Pressure + Bowman’s Capsule Hydrostatic Pressure)

Question 17

Autoregulation

Answer 17

Mechanisms in place to prevent sudden swings in GFR

Myogenic Activity:
Vasoconstriction and vasodilation to control arterial blood pressure and change GFR

Tubuloglomerular Feedback:
- Specializes macula densa cells in the Juxtaglomerular apparatus detect changes in salt levels. More fluid in the distal tubule is detected by a higher level of salt
- The macula densa releases ATP to make adenosine and constrict afferent arterioles
- Reduced GFR

Question 18

Sympathetic Control of GFR

Answer 18

Baroreceptors detect changes in blood pressures
If pressure is low, sympathetic activity constricts afferent arterioles
- this decreases glomerular capillary pressure and GFR

Question 19

The Kidneys and Cardiac Output

Answer 19

The kidneys receive around 22% of the cardiac output

Question 20

Tubular Reabsorption

Answer 20

Two step process:
1. Active or passive movement of substances from the tubule into the interstitial space
2. Passive movement of substances from the interstitial space back into the bloodstream

Question 21

Transepithelial Transport

Answer 21

Movement of solutes across and epithelial cell layer through the cell
- Tight junction prevent the movement between cells

Luminal membrane - beside the tubule lumen
Basolateral membrane - in contact with the interstitial fluid

Question 22

The Steps of Transepithelial Transport

Answer 22

1. The substance must cross the luminal membrane.
2. The substance must pass through the cytosol (cytoplasm).
3. The substance must cross the basolateral membrane.
4. It must diffuse through the interstitial fluid.
5. It must cross the capillary wall to enter the plasma

Question 23

Locations of Sodium Reabsorption

Answer 23

The Proximal Tubule:
76% of sodium reabsorption
- cotransport of other solutes
The Ascending Limp of the Loop of Henle:
25% of sodium reabsorption
- Used to control urine concentration
The Distal and Collecting Tubules:
- Sodium reabsorption is under hormonal control to regulate ECF volume and secretion of K+ and H+

Question 24

Active Transport of Sodium

Answer 24

• Passively diffuse across the luminal membrane
• ATP sodium potassium pumps to cross basolateral membrane
• This transportation uses 80% of the kidneys energy
• Active transport maintains cytosol concentration gradient for passive diffusion

Question 25

Passive Transport of Sodium

Answer 25

Proximal Tubule: - Sodium crosses with cotransporters that simultaneously move organic nutrients - These nutrients used secondary active transport to move along sodiums gradient, against their own Collecting Duct: - Sodium passively enters epithelia cells through sodium channels

Question 26

Hormonal Regulation of Sodium

Answer 26

Within the Juxtaglomerular Apparatus there are granular cells Primary triggers of Renin Secretion 1. Granular cells detect a drop in blood pressure and secrete renin 2. Granular cells innervated by sympathetic nervous system and release renin 3. The Macula densa sense a decrease in luminal Na+, and trigger the granular cells to secrete renin

Question 27

Renin and Sodium

Answer 27

Renin: - Acts like an enzyme to convert angiotensinogen* into angiotensin I. Angiotensin-converting enzyme: When circulating angiotensin I passes through the lungs, it is converted to angiotensin II by the enzyme angiotensin converting enzyme (ACE). Angiotensin II: Angiotensin II, in turn, stimulates the adrenal cortex to release aldosterone. Aldosterone: Aldosterone then causes an increase in Na+ reabsorption in the distal and collecting tubules.

Question 28

Atrial Natriuretic Peptide

Answer 28

ANP release reduces sodium load and blood pressure - Increase in blood volume of increase venous return is detect by artery stretch receptors and trigger ANP release 1. It directly inhibits Na+ reabsorption in the distal tubules so there is more Na+ excreted in the urine. 2. It inhibits both renin and aldosterone secretion. 3. It dilates the afferent arterioles and increases GFR. As more salt and water are filtered, more salt and water are excreted

Question 29

Active Reabsorbed Substance

Answer 29

Substances actively reabsorbed have specific carrier proteins Tubular/Transport maximum - limited number of carrier proteins so there is a limited about of substance reabsorbed Renal Threshold - exceeding the transport maximum so the excess substance is excreted

Question 30

The Hormonal Control of Phosphate

Answer 30

1. A fall in plasma phosphate increases plasma calcium, which directly suppresses P T H secretion. In the presence of reduced P T H, phosphate reabsorption by the kidneys increases, returning plasma phosphate concentration toward normal. 2. A fall in plasma also increases activation of vitamin D within the kidney, which then promotes absorption in the intestine.

Question 31

Filter Load

Answer 31

The amount of substance that entires the bowman's capsule Filtered load = plasma concentration x GFR

Question 32

Glucose

Answer 32

In the case of glucose, its normal Tm is 375 m g/min. This means that for all filtered loads of glucose below 375 m g/min, 100% of the glucose will be reabsorbed. Only when the filtered load of glucose exceeds 375 m g/min will glucose appear in the urine.

Question 33

Water Absorption

Answer 33

Water is passively reabsorbed by following sodium (osmosis). Reabsorption by location: Proximal tubule: ~65% Loop of Henle: ~15% Distal + collecting tubules: ~20% Reabsorption in the proximal tubule and loop is constant. Reabsorption in the distal/collecting tubules is variable, depending on: Hormones (vasopressin/ADH) Hydration level Water moves through aquaporins: Always open in proximal tubule Regulated by vasopressin in distal tubule Reabsorption is driven by: Sodium gradients Plasma oncotic pressure in capillaries

Question 34

Chloride Absorption

Answer 34

Not directly regulated by the kidneys. Reabsorbed passively between cells (paracellular route). Moves down its electrochemical gradient. Amount reabsorbed depends on sodium reabsorption.

Question 35

Urea Absorption

Answer 35

Waste product, but significant amounts are reabsorbed. Initially same concentration as plasma → no net movement. As water is reabsorbed, urea concentration increases, causing passive reabsorption. Only 40–50% of filtered urea is excreted. Blood urea nitrogen (BUN) is used clinically: High levels indicate reduced kidney function (renal failure).

Question 36

Tubular Secretion

Answer 36

Movement of substances from the peritubular capillaries to the tubule lumen - Additional removal of substances - Substances included hydrogen ions, potassium ions, organic anion and cations, and other foreign substances

Question 37

Hydrogen Ion Secretion

Answer 37

Secreted in the proximal, distal and collecting tubules - The amount secreted depends on the acidity of the plasma (high H+ means more secreted) - Helps regulate acid-base balance

Question 38

Potassium Ion Secretion

Answer 38

Freely filtered at the glomerulus and actively reabsorbed in the proximal tubule - Elevated plasma potassium is secreted into the distal and collecting tubules - The absorption in the proximal tubules and generates a concentration gradient for potassium to pass through channels in the luminal membrane into the tubular fluid

Question 39

Control of Potassium Secretion

Answer 39

Sodium: Increase in sodium reabsorption in turn causes more potassium secretion - Decrease plasma sodium, ECF volume and arterial blood pressure stimulates abnormal potassium secretion Effect of Hydrogen Secretion: - The Na+ -K+ -ATPase pump on the basolateral membrane of the distal sections of the nephron can readily substitute H+ for K+ - interstitial concentration of one of these ions increases, it can decrease the rate at which the other is transported

Question 40

Secretion of Organic Anions and Cations

Answer 40

Two secretory carriers, one for anions and another for cations - Tubular secretion increases organic ion excreted - Usually carrier bound so can't enter the glomerular filtrate

Question 41

Plasma Clearance

Answer 41

Volume of plasma cleared of that substance by the kidneys per minute Clearance rate (m l/min) = urine concentration (quantity/m l) x urine flow rate (m l/min) / plasma concentration (quantity/m l)

Question 42

Types of Plasma Clearance

Answer 42

Substances filtered not reabsorbed: - Insulin is freely filtered but not secreted or reabsorbed so its excretion is 100% Substances filtered and reabsorbed: -Glucose is freely filtered but has a high reabsorbance so its plasma clearance is 0 - Urea is partially reabsorbed so it has a plasma clearance of 62.6 Substances that are filtered and secreted by not reabsorbed: - Hydrogen

Question 43

Vertical Osmotic Gradient

Answer 43

Moving from the cortex to the renal pelvis, there is a gradual gradient as the interstitial fluid osmolarity increases

Question 44

The Medullary Vertical Osmotic Gradient

Answer 44

1. In proximal tubule, strong drive for osmotic reabsorption of water and sodium 2. 65% of filtrate volume reabsorbed in proximal tubule. Tubular fluid is still isotonic 3. Descending loop of henle impermeable to water but not sodium and vice versa in ascending loop - tubular fluid always for hypotonic than interstitial fluid

Question 45

Vasopressin Controlled Water Reabsorption

Answer 45

1. Released from posterior pituitary gland when ECF is hypertonic 2. Acts on distal tubular cells to increase number of aquaporin molecules in luminal membrane 3. Water passively moves into interstitial fluid and plasma

Question 46

Vasa Recta

Answer 46

- Highly permeable to NaCl and water - Bloodflow is opposite to the fluid flow through the loop of henle - Maintains osmolarity in contrast to loop of henle

Question 47

Diruresis

Answer 47

Osmotic Diuresis: Increased excretion of both water and excess unreabsorbed solute Water Diuresis: Increases excretion of water with no change in solute excretion - ex. alcohol consumption

Question 48

Urine Storage

Answer 48

Bladder: - Smooth muscle so can stretch - innervated by parasympathetic system to cause contractions Internal Urethral Sphincter: - Involuntary control - When bladder is relaxed, outlet of urethra is closed External Urethral Sphincter: - Closed by constant nerve firing - Can be deliberately tightened to prevent urination