(PCT)
PROXIMAL CONVOLUTED TUBULE

ARCUATE VEIN

(1) (DCT) Macula Densa Cells
--> chemoreceptors/osmoreceptors
sense low Na+/Cl- levels

(2) Extraglomerular Mesangial Cells
--> help send message from the DCT (Mac. Densa) to the Jixta. cells
--> "extra" = outside/not directly beside Glomerulus
--> "Mesangial" = messengers between Macula Densa and Juxtaglomerular cells

(3) Juxtaglomerular/Granular Cells (PCT)
--> mechanoreceptors
sense low blood pressure
--> also recieve signal of
low Na+/Cl- from DCT
--> release renin (angiotensin pathway)
--> aldosterone, ADH, reabsorption effects

Notes:

(1) Nephrons are of 2 types:

• Cortical Nephrons

  
  

  --> 85% of nephrons

  
  

  --> short Loop of Henle

  
  

• Juxtamedullary Nephrons

  
  

  --> produce concentrated urine

  
  

  --> LONG Loop of Henle

  
  
  

(2) GFR

• average GFR=120 in range of 90-140 (ml/min)
• 120/600 = 20% of blood filtered at Glomerulus
• blood plasma is filtered approx. 60 times/day
  
  

(3) Freely-filtered substances

• DOES NOT mean all of the substance is filtered
• means that the filtered plasma contains
  same concentration as in the unfiltered plasma
  
  

(4) Juxtaglomerular Complex

• Communication between the DCT and the afferent arteriole
  --> afferent arteriole: best measure of bp in the body entering kidney
  --> DCT: best measure of solute filtration after most reabsorption has already occured
• In actuality, the renal corpiscle should face the distal tubule
  to receive signals from the DCT Macula Densa Cells
  
  

(5) 3 Layers of Glomerular Filtration

• Layer 1: vascular endothelial layer
  --> single squamous cell layer
  --> fenestrated with microscopic pores (~70 nm diameter)
• Layer 2: basement membrane
  --> non-cellular [Collagen and Glycoproteins (fibronectin and laminin)]
  --> (-) charge on Glycoproteins repels (-) charged proteins (albumin)
• Layer 3: visceral epithelial layer of B. capsule = podocytes (fingers)
  --> "podo" means foot --> foot cells (~25-40 nm diameter)
  --> slit diaphragms between the podocytes have (~8 nm diameter) pores
  
  

(6) Glomerular Filtration

• Passed through filter:: Water, Electrolytes, Glucose, Amino acids,
  Fatty acids, Vitamins, Urea, Uric acid, Creatinine
  --> (+) molecules > (-) molecules
• Turned Back:: RBCs, Plasma proteins, Large anions,
  Protein bound minerals and hormones
  --> Albumin: small enough (6 nm diameter), but (-) charge
  
  

(7) Minimal Change Nephropathy

• lose (-) charge on the basement membrane layer
  (even before histology changes noticed)
• allows smaller (-) charged proteins like albumin/transferrin to pass filtration
• leads to proteins in the urine --> proteinuria or albuminuria
  
  

(8) (PCT) PROXIMAL CONVOLUTED TUBULE

• Main site of Reabsorption
• Large surface area: lots of vili

• Transport abilities: many vesicles to transport,

  
  

  many mitochondria for ATP to transport

  
  

• Na+ moves into the cell and down its electrochemical gradient coupled to:

  
  

  (glucose, amino acid, phosphate, lactate, or citrate), which move into the cell against their electrochemical gradients

  
  
  

(9) LOOP OF HENLE

• Thin limb
  --> thin squamous cells : osmosis of water
• (TAL) Thick Ascending Limb
  --> many mitochondria and vesicles for transport of ions
  
  

(10) (DCT) DISTAL CONVOLUTED TUBULE

• Main site of Secretion into Tubule
• Cuboidal cells without microvilli secrete contents
  
  

Descending
Vasa
Recta

• high resistance
• low blood flow to
  maintain
  hyperosmotic medulla

Notes (continued):

(11) COLLECTING DUCT

• Main site of Reabsorption
  
  

(12) O2 Consumption Dependent on Blood Flow

• In all other organs, blood flow is dependent on O2 consumption (ex: muscles)
• In kidneys, same correlation, but opposite causal effect
• O2 consumption dependent on the Na+ reabsorption and H+ATPase pumps,
  which is determined by the blood flow to the kidney
  
  

(13) Blood Flow in Kidney

• Cortex: gets 90% of blood flow to kidney
• need low blood flow to the medulla to maintain hyperosmolarity
  (otherwise blood would reabsorb the solutes from interstitium)
• allows juxtamedullary nephrons to produce highly concentrated urine
  
  

(14) Capillary Beds in the Kidney

• Systemic Capillary Beds:
  --> filtration at the arterioles
  --> reabsorption at the venules
• Peritubular Capillary Beds:
  --> reabsorption at the arterioles
  --> filtration at the venules
• Kidney's 2 Capillary Beds in Series:
  --> major filtration at Glomerulus capillary bed
  --> major reabsorption at peritubular capillary beds
  
  

(15) Pressure Control in the Kidney

• Afferent Arteriole Constriction:
  --> Glomerulus pressure decreases
  --> Peritubular pressure also decreases
  --> Both afferent/efferent constriction decrease RPF
• Efferent Arteriole Constriction:
  --> Glomerulus pressure increases
  --> Peritubular pressure decreases
  --> Both afferent/efferent constriction decrease RPF
  
  

(16) Innervation of the Kidney

• NO Parasympathetic innervation
• Sympathetic innervation:
  --> Main effect is to increase Blood Pressure
  --> Juxtaglomerular/Granular Cells: causes renin release
  --> All other parts of Nephron: causes Na+ reabsorption
  
  

(17) Autoregulation of the Kidney

• intrinsic autoregulation:
  --> occurs when: 80 < MAP < 180
  --> done by constriction/resistance in the afferent and efferent arterioles
  --> renin/angiotensin system
  --> angiotensin 2 only causes constriction in the EFFERENT ARTERIOLE
  --> prostaglandins (in both), but mainly dilation in the AFFERENT ARTERIOLE
• Extrinsic autoregulation:
  --> occurs when: MAP < 80
  --> sympathetic hormones override the intrinsic controls
  --> primarily cause vasoconstriction in the AFFERENT ARTRIOLES
  
  

(18) Ion Exchanegs

• K+ moves in opposite directions as H+/Na+
• Paracellular Pathways:
  --> only positive ions (besides H+):
  Mg2+, Ca2+, Na+, K+
• Na+ always done by Active Transport

Pharmacology Notes:

(1) Probenecid

• increases the excretion of uric acid
• blocks tubular excretion of penicillins
• increases serum levels of both furosemide (loop diuretic) and Heparin

Notes (continued 2):

(19) 3 Layers of Tubular Transport

• luminal membrane of renal tubule
  = apical membrane
• basolateral membrane of renal tubule
• peritubular capillary endothelium
  
  

(20) Reabsorption

• Most substances which are reabsorbed are 98-100% reclaimed. Notable
• exceptions are potassium (86%, variable) and urea (50%, variable).
  
  

(20) Sodium Reabsorption

• PCT
  --> H+/Na+ antiporter
  --> Na+/Cl- through paracellular transport
  --> 65-70% of Na+ reabsorbed
• TAL
  --> Na+/2Cl-/K+ symporter
  --> 25% of Na+ reabsorbed
• DCT
  --> Na+/Cl- symporter
  --> 5% of Na+ reabsorbed

RAAS (SNS) SYSTEM
(= renin-angotensin-aldosterone system)

• SNS is the main factor that stimulate the release of Renin from Glomerular afferent granular cells
  --> renin starts the RAAS system
  --> Beta 1 receptors causes renin release
• renin also released due to DCT Mac Dens --> Juxta-messangial cells sensing low Na+ and low ECV
• Angiotensin 2 mainly constricts the efferent arteriole, although it does both
  --> increases the GFR
• Angiotensin 2 also stimulates Aldosterone release
• aldosterone acts on the DCT and collecting ducts to
  --> reabsorbs Na+
  --> excretes K+ and H+
• ADH ALWAYS follows Aldosterone release (main factor)

ANP (PNS) SYSTEM

• works agianst ADH and the RAAS system
• right atrium of heart mechanoreceptors sense high BP
  --> release ANP = atrial naturetic peptide
• 2 main goals of ANP mediated through the kidney
  --> increase Na+ excretion
  --> decrease Aldosterone
• decrease Na+ excretion
  --> dilate afferent and constrict efferent to increase GFR and filter more Na+
  --> decrease sodium reabsorption
• decrease aldosterone
  --> decrease renal renin release