4a: Renal, nephron structure, renal blood flow, glomerular filtration

Renal Physiology

Learning Outcomes

• Produce a diagram showing the structures and major functions of the nephron.

• Explain the relationship between renal blood flow and glomerular filtration rate.

• Discuss the role of the sympathetic nervous system in the regulation of renal blood flow.

• Describe the role of the renin-angiotensin system as it relates to renal blood flow.

• List several factors that affect glomerular filtration rate.

Functions of the Kidneys

• The kidneys have numerous functions beyond urine production:
      - Key role in regulating blood pressure.
      - Produce erythropoietin vital for red blood cell production.
      - Maintaining calcium and phosphate balance via nephrons and Vitamin D activation.
      - Maintaining acid/base balance.
      - Maintaining electrolyte balance such as potassium and sodium.
      - Removal of waste products including urea, creatinine, drugs, and toxins.

Kidney Anatomy Overview

Components of the urinary system (urine formation and excretion):

• Ureter

  • muscular tube connecting kidney to bladder

  • uses peristalsis to push urine to bladder

  • prevents backflow with one-way flow dynamics

  • peristalsis: involuntary constriction and relaxation of the muscles of a canal, creating wave-like movements that push content forward

• kidney

  • filters blood

  • remove waste

  • regulates electrolytes

  • maintains acid-base balance

  • controls blood pressure (via renin

  • produces hormones

• bladder

• urethra

  • lined with mucosa (protective, mucus-secreting liner of hollow organs. shields bladder and urethra from urine while allowing stretch and smooth flow)

  • surrounded by sphincters (specialised ring-shaped muscle)

  • internal urethral sphincter (smooth, involuntary)

  • external urethral sphincter (skeletal muscle, voluntary)

• nephron (enlarged)

  • the functional unit of the kidney (~1 million per kidney)

  • filtration (glomerulus)

  • reabsorption (proximal tubule, loop of henle, distal tubule)

  • secretion (distal tubule)

  • concentration (collecting duct)

• minor calyx

  • a small cup like structure that collects urine from one papilla

  • passes it into a major calyx

• major calyx

  • formed by merging several minor calyx

  • channels urine toward the renal pelvis

• papilla

  • tip of each renal pyramid

  • where urine exits the medulla

  • drains into the minor calyx

  • the first point where fluid is officially “urine”

• renal cortex

  • outer region of kidney, (but within the capsule)

  • contains most of the nephrons

  • where blood first becomes “filtrate”

  • primary site of filtration and initial urine formaion

• renal pelvis

  • funnel shaped reservoir inside the kidney

  • collects all urine from the major calyces

  • narrows to become the ureter

• renal medulla

  • contains loops of henle/nephron loops and collecting ducts

  • preserves water

  • creates osmotic gradient to concentrate urine

• renal pyramid

  • cone shaped section OF the medulla

  • houses loops of henle and collecting ducts

  • transports urine from nephrons to papilla “urine funnels”

• capsule of kidney

  • tough fibrous outer layer

  • protects kidney from trauma

  • maintains shape

  • acts as barrier against infection spreading into the kidney

Structure of the Nephron

• The nephron is the basic functional unit of the kidney.

• Approximately 1.3 million nephrons per kidney.

glomerulus: a tuft of capillaries inside bowman’s capsule

proximal convoluted tubule (PCT)

Alternative Diagram of Nephron

Key Structures filtrate - small solutes filtered out of the glomerulus

• Cortex:

  • glomerulus (inside bowman’s capsule)

    • performs filtration

    • blood pressure forces water + small solutes out of the blood

    • large proteins and cells stay in the bloodsteream

  • bowman’s capsule

    • surrounds the glomerulus

    • collects the filtrate produced by the glomerulus

    • funnels it into the proximal tubule

  • proximal convoluted tubule (PCT)

    • highly folded segment of the tubule

    • “workhouse” of the nephron

    • reabsorbs most of filtered water and Na

    • reabsorbs all glucose and amino acids

    • secretes some wastes (H, drugs)

  • distal convoluted tubule (DCT)

    • more selctive, hormune-regulated segment

    • fine-tunes electrolyte balance

    • reabsorbs Na

    • regulates Ca

    • secretes H and K

  • macula densa

    • specialised grouop of DCT cells that sense NaCl in the filtrate and adjusts GFR and renin release to maintain stable kidney function

  • connecting tubule

  • cortical collecting tubule

    • determines final urine concentration

    • rebasorbs water

    • reabsorbs Na

    • carries urine through the medulla to papilla to calyces

• Medulla:

  • loop of henle: overall, creates the medullary osmotic gradient (concentrates the medulla) which allows the kidney to produce concentrated urine.

    • descending limb first: permeable to water, not permeable to solutes. water leaves, filtrate becomes more concentrated

    • thick segment of ascending limb

    • thin segment of ascending limb

    • ascending limbs: permeable to solutes (Na, K, Cl). not permeable to water. solute leave. filtrate become more dilute

  • medullary collecting tubule

  • collecting duct

Renal Blood Flow (RBF)

Key components:

• interlobar arteries and veins

  • between lobes

• renal artery

  • blood comes in from here

• renal vein

  • blood goes out form here

• segment arteries

  • arteries that are brnched off

• afferent and efferent arteriole

  • afferent before glomerulus

  • efferent after glomerulus

    - Interlobar arteries and veins
    - Renal artery and vein
    - Segmental and arcuate arteries and veins
    - Interlobular arteries and veins
    - Peritubular capillary network
    - Urine flows into renal papilla

The Renin-Angiotensin System (RAS)\

• a hormonal system that regulates:

  • blood pressure

  • fluid balance

  • electrolyte homeostasis

• Processes:
      1. Drop in blood pressure
      2. Drop in fluid volume
      3. Renin release from kidney
      4. Renin acts on angiotensinogen (produced by the liver) to form angiotensin I.
      5. ACE (angiotensin-converting enzyme) released from lungs converts angiotensin I to angiotensin II.
      6. Angiotensin II effects:
          - Vasoconstriction of blood vessels.
          - Acts on the adrenal gland to stimulate release of aldosterone.
          - Aldosterone acts on kidneys to stimulate reabsorption of sodium chloride (NaCl) and water (H₂O).

Urine Formation - Overview

1. Filtration:
       - Blood is filtered in the glomerulus (coming in afferent, exiting efferent), removing waste and excess fluid.

2. Reabsorption:
       - Essential substances are reabsorbed into the blood (to be covered in Lecture 2).

3. Secretion:
       - Additional toxins and ions are actively removed (to be covered in Lecture 2).

4. Excretion:
       - Final urine is collected and eliminated from the body (to be covered in Lecture 2).

urine excretion rate = filtration rate - reabsorption rate + secretion rate

Glomerular Filtration – Cell Membrane

• Working from the inside out, the capillary walls consist of three layers:
      - Endothelium

• larger pores

• solutes, plasma can pass through but not blood cells
      - Basement membrane
      - Epithelium

Glomerular Filtration – Permeability

• Permeability metrics:
      - Glomerular capillary is 50 times more permeable than skeletal muscle capillary. (very very permeable)
      - Selective permeability based on:
          - Size
          - Charge (likes neutral molecules more than anionic and cationionic)
      - For neutral molecules:
          - Less than 4.0 nm is freely filterable.
          - More than 8.0 nm is almost non-filterable.

Glomerular Filtration Rate (GFR) Control

• Note: There is a Bowman's colloidal osmotic pressure, but it usually is 0 mm Hg; thus, it is often omitted in equations.

• In certain disease states, the presence of proteins in the Bowman's capsule can raise this pressure above 0 mm Hg.

• rate at which the kidneys filter blood

• net filtration pressure = glomerular hydrostatic pressure - bowman’s capsule pressure (~18 mm Hg) - glomerular colloid osmotic pressure (usually 32 mm Hg)

• glomerular hydrostatic pressure:

  • pressure of the blood as it forces its fluid into the bowman’s capsule

  • ~60 mm Hg

• bowmans colloidal osmotic pressure, usually 0mm Hg unless disease present

Factors That Affect GFR

1. Changes in filtration coefficient (Kf):
       - Filtration coefficient (Kf):
         - Defined as the product of a biological membrane's permeability to water and the surface area of the membrane.

2. Changes in glomerular capillary hydrostatic pressure (GCHP)

3. Changes in Bowman's capsule hydrostatic pressure (BCHP)

4. Changes in glomerular colloidal osmotic pressure (GCOP)
       - Notably, changes in Bowman's colloidal osmotic pressure

Factors That Affect GFR – Filtration Coefficient (Kf)

• affected by Surface Area of the Glomerular Membrane:
      - Increase in surface area (↑ surface area) leads to (↑ Kf) and subsequently (↑ GFR).
      - Relaxation of mesangial cells increases surface area.

• 
      - Decrease in surface area (↓ surface area) leads to (↓ Kf) and subsequently (↓ GFR), connected to:
          - Contraction of mesangial cells.
          - Decreased number of glomerular capillaries.
          - Uncontrolled diabetes impacting Kf.
      

• affected by Permeability of Glomerular Membrane:
          - Increase in thickness (↑ Thickness) leads to (↓ Kf) and subsequently (↓ GFR) (impacted by uncontrolled diabetes and hypertension).

Factors That Affect GFR – Glomerular Capillary Hydrostatic Pressure

• Effects of Vasodilation vs. Vasoconstriction:
      - Vasodilation leads to (↑ GCHP) which elevates (↑ GFR).
      - Vasoconstriction leads to (↓ GCHP) reducing (↓ GFR).
      - Initial vasoconstriction raises GCHP, potentially leading to increased GFR, but excessive vasoconstriction decreases renal blood flow (RBF) and decreases GFR.
      - Hormonal and neural control:
          - Integrated with autoregulation mechanisms, including myogenic regulation.

• blood pressure

• tubuloglomerular feedback

• hormonal and neural control

blood pressure provides the driving force

tubuloglomerular feedback stabilises GFR locally

hormonal/neural systems adjust afferent and efferent arterioles to raise or lower GFR depending on the body’s needs

Factors That Affect GFR – Bowman's Capsule Hydrostatic Pressure

• Urinary Obstruction:
      - Increased Bowman's capsule hydrostatic pressure (BCHP) leads to decreased GFR.
      - Common examples include:
          - Kidney stones.
          - Prostate enlargement.

Factors That Affect GFR – Glomerular Colloidal Osmotic Pressure

• Effects of Changes in GCOP:
      - An increase in GCOP (↑ GCOP) results in a decrease in GFR (↓ GFR).
          - Example: Dehydration increases GCOP.
      - A decrease in GCOP (↓ GCOP) results in an increase in GFR (↑ GFR).
          - Example: Hypoproteinemia.

glomerular hydrostatic pressure pushes filtrate out

capsule pressure and glomerular oncotic pressure pushes back in

bowmans oncotic pressure is normally 0 because proteins don’t filter.