renal 2

Recap of Kidney Functions

  1. Homeostatic Control of ECF Volume, Ionic Composition, & Blood Pressure

    • Balances water and electrolytes (e.g., Na+, K+, Ca2+)

    • Fluid volume affects Stroke Volume (SV) and Mean Arterial Pressure (MAP)

    • Related structures: 12th rib, renal capsule

  2. Excretion of Wastes

    • Removes metabolic wastes (e.g., urea), drugs, and toxins from the body.

  3. Endocrine Function

    • Secretion of hormones: Renin, Erythropoietin (EPO), and Vitamin D3

  4. pH Regulation

    • Regulation occurs through the reabsorption and/or secretion of bicarbonate (HCO3-) and hydrogen ions (H+).

Structure of the Kidney

  • Kidney Shape: Bean-shaped with two layers.

    • Outer Layer: Renal cortex

    • Inner Layer: Renal medulla

  • Functional Unit: Nephron; the smallest structure capable of performing the functions of the kidney.

Anatomy of the Nephron

  • Nephron Types:

    • Cortical Nephron: Predominantly in the cortex.

    • Juxtamedullary Nephron: Extends into both layers (cortex and medulla).

  • Key Structures:

    • Renal corpuscle

    • Renal tubules (comprising proximal convoluted tubule, Loop of Henle, distal convoluted tubule)

    • Collecting duct which leads to the renal pelvis.

  • Surrounding Structures:

    • Ureter, minor and major calyx, renal pyramid, and renal papilla.

Maintaining Homeostasis: Processes in the Nephron

  1. Filtration:

    • Pressure pushes fluid from blood into nephron (into Bowman’s capsule).

    • Nephron described as a hollow tube (lumen).

  2. Reabsorption:

    • Movement of solutes & H2O from nephron back to blood.

    • Process is selective; termed 'reabsorption' because substances were once in the body.

  3. Secretion:

    • Movement of solutes & H2O from blood to nephron.

Anatomy of Nephron Tubules

  • Nephron tubules are typically intertwined and folded, surrounded by capillaries to facilitate reabsorption of water and ions.

  • For clarity, images of unfolded nephron tubules are discussed for educational purposes.

Wastes Excretion

  • Any substances remaining in nephron will be excreted as waste.

  • Excretion Defined: Movement of metabolic and dietary waste products from the lumen of the nephron to outside the body (urine formation).

    • Example waste products include: urea (from protein metabolism), bilirubin, surplus H2O, ions, and creatinine.

  • Key Principle: Anything that the body needs to retain must exit the nephron; anything that needs to be excreted must remain within the nephron.

Blood Flow and Nephron Interaction

  • Blood Flow Components:

    • Afferent arteriole

    • Glomerular capillaries

    • Efferent arteriole

    • Peritubular capillaries and vasa recta

    • Venous circulation.

Filtrate Flow Through Nephron

  1. Bowman's Capsule (glomerular capsule)

  2. Proximal Convoluted Tubule (PCT)

  3. Loop of Henle (divided into descending and ascending loops)

  4. Distal Convoluted Tubule (DCT)

  5. Collecting Duct (CD)

Filtration Dynamics

  • Filtering primarily allows only small molecules; larger molecules and proteins are retained in the blood due to structure and function of glomerular capillaries and the help of podocytes.

Capillary Pressures

  1. Hydrostatic Pressure:

    • Generated by the heart (also referred to as blood pressure)

    • Responsible for pushing fluid out of the capillary into the interstitial fluid (ISF).

  2. Colloid Osmotic (Oncotic) Pressure:

    • Generated by plasma proteins, originating from the liver.

    • Pulls water back into capillaries via osmosis.

Calculating Filtration Pressure

  • Pressures Involved:

    • Hydrostatic pressure (HP) in glomerular capillaries: 55 mmHg

    • Colloid pressure from plasma proteins: 30 mmHg

    • Capsule pressure (from fluid in Bowman’s capsule): 15 mmHg

  • Net Filtration Pressure:

    • Calculated as: (Net Pressure = HP - (Colloid Pressure + Capsule Pressure) = 55 - (30 + 15) = 10 \, mmHg)

Clinical Implications: Clicker Check

  • Question posed regarding the implications of protein leakage in glomerular filtration — effects on hydrostatic and colloid pressures.

  • Example scenarios involving patients with untreated end-stage renal disease and occurrence of edema discussed.

Glomerular Filtration Rate (GFR)

  • Definition: GFR is the volume of fluid entering Bowman’s capsule per unit of time.

  • Average GFR: 125 mL/min, equating to 180 L/day.

  • Only about 1-2 L of urine is produced, reflecting a reabsorption rate of approximately 99% of the filtered fluid.

Regulation of GFR

  • Afferent Arteriole State: Changes in the contraction of the afferent arteriole alter renal blood flow (RBF) and consequently the GFR.

    • Vasodilation:

    • Increases renal blood flow ⇒ increases hydrostatic pressure ⇒ increases GFR ⇒ increases urine output.

    • Vasoconstriction:

    • Decreases renal blood flow ⇒ decreases hydrostatic pressure ⇒ decreases GFR ⇒ decreases urine output.

Hormonal Regulation of GFR

  1. Vasoconstrictors (Decrease GFR):

    • Sympathetic stimulation (alpha adrenergic receptors)

    • ADH (Antidiuretic hormone)

    • Angiotensin II (ANG II)

  2. Vasodilators (Increase GFR):

    • Atrial Natriuretic Peptide (ANP)

Atrial Natriuretic Peptide (ANP)

  • Mechanism: Released in response to increased blood volume and atrial stretch.

  • Effects on blood volume:

    • Induces vasodilation

    • Increases urine output, thereby reducing blood volume and MAP (Mean Arterial Pressure).

Response to Small Changes in MAP

  • Self-regulation via Tubuloglomerular Feedback is discussed as a mechanism to maintain GFR in the face of ordinary fluctuations in MAP.

  • Mechanism:

    • DCT via macula densa cells sensing filtrate flow and sending paracrine signals to the afferent arteriole to either vasodilate or vasoconstrict based on filtrate flow rate.

Tubuloglomerular Feedback Summary

  • If filtrate flow is too fast:

    • Afferent arteriole vasoconstricts to decrease filtrate flow.

  • If filtrate flow is too slow:

    • Afferent arteriole vasodilates to increase filtrate flow.

Detailed Overview of Nephron Reabsorption

  1. Filtration: Pressure pushes fluid from blood into the nephron.

  2. Reabsorption: Solutes & H2O are moved back into blood, making this process selective.

Glucose Reabsorption in Proximal Convoluted Tubule (PCT)

  • Approximately 70% of Na+ and 100% of glucose are reabsorbed in the PCT.

  • Mechanism: Glucose is only reabsorbed in the PCT via sodium-glucose transporters (SGLT).

    • Na+ follows its gradient into the cell, glucose follows via secondary active transport.

  • Medications: SGLT inhibitors used for managing Type II diabetes to prevent excessive glucose reabsorption.

Implications of Glucose in Filtrate

  • If glucose is not reabsorbed, the osmotic pressure increases, leading to less water being reabsorbed, thereby increasing urine output (polyuria).

Importance of Water Reabsorption

  • Water movement by osmosis is crucial to prevent dehydration.

  • Water follows solutes based on the concentration gradient and membrane permeability.

Summary of Transport in the PCT

  • Low intracellular Na+ concentration is maintained by the Na/K ATPase pump, promoting Na+ entry into the cell from the lumen, facilitating glucose reabsorption.

  • At peritubular capillaries, solutes move from Interstitial Fluid (ISF) into the blood via simple diffusion due to the concentration gradient.