2- Kidney Function

Renal autoregulation

maintains constant blood flow and glomerular filtration rate despite fluctuations in blood pressure

• operates effectively within mean arterial pressure of 80-100 mmHg

• myogenic mechanism and tubuloglomerular feedback

Myogenic mechanism

• rapid

• triggered by high arterial pressure, stretching walls of afferent arteriole

• stretching affects mechanosensitive ion channels, depolarizing membranes, ↑ calcium concentration

• ↑ smooth muscle contraction, ↑ resistance,

Tubuloglomerular feedback

• slower

• specialized macula densa cells in juxtaglomerular apparatus sense ↑NaCl

• ↑paracrine signaling molecules from macula densa, which bind to receptors on afferent arteriole and cause it to constrict

4 functions of the kidney

1. filtration

2. reabsorption

3. secretion

4. elimination

Glomerulus

tuft of capillaries responsible for filtering blood

Glomerulus cell type

capillary endothelial cells

• fenestrated, allow for easy passage of water ions and small molecules

• retains larger proteins/blood cells

Bowman’s capsule

encases glomerulus

• Bowman’s space

• parietal layer

• visceral layer

Bowman’s space

• between visceral layer and glomerulus

• filtrate collects here before entering renal tubules

Parietal layer

• outer layer of Bowman’s capsule

• squamous epithelial cells

• structural support, no filtration, maintains shape

Visceral layer

• inner layer composed of podocytes

• interdigitating foot processes wrap around capillary loops of glomerulus

• between foot processes: filtration slits, serving as another barrier to filter blood plasma

Renal corpuscle

filtration of blood to form filtrate, later undergoes further modification in renal tubules

Driving force of renal corpuscle filtration

differing pressures within glomerulus driven by hydrostatic pressure of blood and osmotic pressures within capillaries

3 layers of filtration

1. fenestrated endothelium of glomerular capillaries

2. glomerular basement membrane

3. filtration slits of podocytes

Characteristics of filtration

• highly selective, allowing water, electrolytes, and small molecules to pass into Bowman’s space

• prevents larger molecules and blood cells

Bowman’s capsule epithelium

thin squamous cells continuous with parietal layer

Proximal/distal convoluted tubules and thick limbs of Henle epithelium types

cuboidal/polyhedral granular, nucleated epithelium loosely attached to basement membrane

Collecting tubules epithelium varies

cuboidal epithelium becomes tall and lubricated distally

Absorption in kidneys

65-70% of water, NaCl, potassium glucose, amino acid, and bicarbonate

Pathway of kidney

glomerulus → proximal convoluted tubule → loop of henle → distal convoluted tubule → collecting duct

Proximal convoluted tubule lining

cuboidal epithelium cells with a brush border

• microvilli

• tight junctions - transport

• basolateral membrane - transport proteins/channels

• mitochondria - provides ATP

Proximal convoluted tubule functions

facilitates reabsorption of glucose, amino acids, electrolytes, and water; highly twisted and coiled, maximizing surface area for reabsorption

PCT reabsorption of electrolytes

• Na+ via Na+/K+ pumps

• Cl- electrochemical gradient

• Ca2+, Mg2+, HPO4-

PCT reabsorption of nutrients

glucose and amino acids via Na+-dependent co-transport mechanisms e.g. SGLT2

PCT blood supply

peritubular capillaries - branches of efferent arteries that arise from glomeruli

Loop of Henle structure

• descending LOH

• ascending LOH

  • thin ascending

  • thick ascending

Descending LOH permeability

• permeable to water, allowing reabsorption into medulla

• impermeable to salts & solvents

Descending LOH of juxtamedullary nephrons

longer, extends deeper into medulla than cortical nephrons

Descending LOH epithelium type

simple squamous

• single layer of flat cells

• allows for efficient diffusion

• fewer microvilli

Thin ascending LOH

• simple squamous epithelium

• impermeable to water

• passive diffusion of ions

Thick ascending LOH

• cuboidal epithelial cells with larger number of mitochondria and less brush border

• active in reabsorbing Na+, K+, Cl-

Thick ascending LOH transport

• Na/K/2Cl co-transporter (NKCC2): reabsorbs these 3 ions from tubular lumen into epithelial cells

• active transport: requires ATP, reason for mitochondria

Distal convoluted tubule

selective secretion and reabsorption of ions under hormone control

DCT role in medullary concentration

↑solute reabsorption → ↓tubular fluid osmolarity → ↑medullary concentration

this establishes the renal medulla concentration gradient, aiding in the kidney’s ability to concentrate urine

Collecting duct

fine tunes urine concentration and water reabsorption, regulated by antidiuretic hormone (ADH) and transports filtrate toward renal pelvis

Function of ADH

↑ADH from collecting duct → ↑permeability to water → ↑reabsorption of water back into the blood stream → hydrating the body

Function of aldosterone

↑aldosterone from collecting duct → ↑Na+ reabsorption → K+ secreted into tubular fluid, maintaining electrolyte balance & ↑H2O via osmosis

concentrates urine and regulates blood volume & pressure

Intercalated cells of collecting duct

regulates the body’s acid-base balance by secreting hydrogen ions and bicarbonate; less abundant than principal cells

• type A: secrete H+ and reabsorb HCO3-

• type B: secrete HCO3- and reabsorb H+ (less active)

Principal cells of collecting duct

contain few microvilli that increase surface area for absorption; possess aldosterone and ADH receptors

Secretion

substances move from the blood of the peritubular capillaries into the renal tubules to be excreted as urine

Tubular secretion

happens along the entire renal tubule, primarily from peritubular capillaries into tubules lumen

• moves waste from blood to become urine

• major activity in PCT & DCT

Tubular secretion role in urine secretion

• osmotic gradient established from LOH allows for reabsorption in the collecting duct

• produces hyperosmotic urine in states of dehydration, enabling water conservation

ADH vasopressin role in water reabsorption

↑insertion of aquaporin-2 channels into membranes of kidney tubule cells → ↑water from urine back into the bloodstream

ADH vasopressin role in concentrated urine

↑urine concentration → ↓total volume of urine produced

ADH vasopressin role in BP regulation

constricts blood vessels → ↑peripheral resistance → ↑BP during dehydration/blood loss

Excretion

remaining fluid (urine) moves from tubules into the collecting ducts, renal pelvis, and out of the kidney

Juxtaglomerular cells

• specialized smooth muscle cells located in the walls of afferent arterioles

• synthesize, store, & release renin

Renin

enzyme playing a critical role in BP regulation:

↓BP or ↓NaCl → ↑renin from juxtaglomerular cells → converts angiotensin I to II → vasoconstriction → release of aldosterone → ↑Na+ & H2O reabsorption in kidneys → ↑thirst & ADH

Juxtaglomerular cell appearance

granular due to presence of granules filled with renin

Juxtaglomerular apparatus (JGA)

specialized cell collection, regulates BP and glomerular filtration rate (GFR)

• located at the junction of afferent arterioles and DCT

Extraglomerular mesangial cells

• in the space between afferent & efferent arterioles & glomerulus

• provides structural support

• regulates blood flow and modulates glomerular filtration