Kidney Function and Anatomy

• Kidneys are responsible for filtration, reabsorption, and secretion
• Students should understand the key functions and anatomy of the kidney and nephron
• Students should understand the function of the glomerular filter and the dynamics of ultrafiltration
• Students should be able to describe the processes of tubular reabsorption of glucose and amino acids
• Students should be able to describe the processes of tubular secretion of organic anions and cations

Functions of Kidneys

• Kidneys excrete metabolites or ingested substances from:
  • Protein catabolism (Urea)
  • Nucleic acid breakdown (Uric acid)
  • Muscle creatine (Creatinine)
  • Insulin metabolites (Hormone metabolites)
  • Haemoglobin breakdown (End products)
  • Foreign chemicals e.g. drugs, pesticides
• Kidneys control body fluid composition by:
  • Volume regulation (linked to sodium concentration)
  • Osmoregulation (water balance)
  • PH regulation
• Kidneys have an endocrine component that:
  • Hormones act on
    • Anti-diuretic hormone (ADH)
    • Aldosterone
    • Natriuretic peptides
  • Hormones produced by:
    • Renin

Anatomy of the Kidney

• Kidneys are made up of two parts
  • Cortex (outer)
  • Medulla (inner)
• Urine drains from the kidneys via the ureter to the bladder, which drains via the urethra
• Kidneys contain >1 million nephrons/kidney
• Each nephron contains
  • Renal corpuscle
  • Tubule
• Filtration system and the anatomy of the filtration interface includes:
  • Fenestrated capillary endothelium with pores max size 15nm
  • Basement membrane with fixed polyanions
  • Tubular epithelium (podocytes) with filtration slits around 8nm

Nephron Features

• Bowman's capsule is linked to the renal corpuscle
• Proximal convoluted tubule is linked to the distal convoluted tubule
• Proximal straight tubule is linked to the descending thin limb of Henle's loop
• Ascending thin limb of Henle's loop links to the thick ascending limb of Henle's loop
• Both Medulla and Cortex feed into collecting ducts and eventually the renal pelvis
• Cortical Nephrons (85%) are found in the outer 2/3 of the cortex and have a short Loop of Henle
• Juxtamedullary Nephrons (15%) are found in the inner 1/3 cortex and have:
  • A long Loop of Henle
  • Producing concentrated urine

Juxtaglomerular Apparatus

• Contains a number of cells:
  • Podocytes
  • Extraglomerular mesangial cells
  • Juxtaglomerular cells (includes granular cells)
  • Afferent arteriole
  • Smooth muscle cells
  • Macula densa (Beginning of distal tubule)
  • Sympathetic nerve fibres

Nephron Blood Supply

• Each nephron has 2 sets of arterioles (afferent and efferent)
• Each nephron has 2 sets of capillary beds (glomeruli and peritubular) in series

Renal Processes

• The basic renal processes includes:
  • Glomerular Filtration
  • Tubular Reabsorption
  • Tubular Secretion
  • Metabolism e.g. glutamine
• Each of the processes of filtration, secretion and reabsorption have an:
  • Artery
  • Bowman's space
  • Tubule
  • Peritubular capillary
  • Vein
  • Urinary excretion
• The relations between these processes can be expressed as an equation:
  • amount excreted in urine = amount filtered + amount secreted - amount reabsorbed

Glomerular Filtration Characteristics

• Most plasma constituents are freely filtered except proteins
• Filtration depends on molecular size, charge and possibly shape
• Filtration by size is measured in kD and molecular radius
• Filtration rate will be different based on molecular charge of filtered products
• In the ultrafiltrate:
  • Cells and large proteins are not normally filtered across the filtration barrier
  • Certain drugs and certain ions can bind to proteins, not be freely filtered
  • 40% of plasma Calcium is bound to plasma proteins, so only 60% of plasma Calcium can be freely filtered Glomerular filtration rate (GFR)
  • Is a volume of fluid filtered from the glomeruli per minute (ml/min)
  • Depends on a combination of:
    • Net filtration pressure
    • Permeability characteristics
    • Surface area
  • Is regulated by both neural and hormonal input
  • Has increased excretion of salt and water when there is an elevated GFR
• Filtration depends on:
  • Hydrostatic pressure difference & Colloid osmotic pressure difference
  • Plasma flows across a capillary wall:
    • From a high to a low hydrostatic pressure
    • From a low to a high colloid osmotic pressure
• Starling forces in the filtration equation
  • Hydrostatic pressures (60 mmHg -15mmHg)
  • Colloid Osmotic/Oncotic pressures (29mmHg -0 mmHg)
• Net glomerular filtration pressure = (60-15)-(29-0) = 16 mmHg
• Permeability characteristics of filtration interface
  • Glomerular capillaries: 15nm
  • Majority of other capillaries including peritubular capillaries: 5-12nm
• Surface area of filtration interface Changeable:Intraglomerular mesangial cells
• Normal GFR is 125 ml/min of filtrate formed which is approximately 180 l/day
• Normal liters/day filtered is much higher than other capillaries
• Urine output typically 1.5 liters/day because reabsorption occurs
• Around 99% of filtered water is reabsorbed

Reabsorption of Glucose and Amino Acids

• Happens at the proximal tubule
• Luminal includes:
  • membrane of tubule cells
  • faces filtrate.
• Basolateral membrane includes:
  • faces peritubular capillary.

Proximal Tubule characteristics

• Walls are a single layer of columnar cells
• Contains a luminal membrane
• Also encompasses microvilli and mitochondria
• Organic nutrients are driven by:
  • Na+-coupled co-transporter
  • Tubular maximum (Tm) system
  • Specific Transporters

Glucose Reabsorption

• Filtered glucose can be reabsorbed completely normally
• Glucose is facilitated by 2 types of transporters
  • Sodium-dependent glucose co-transporter (SGLT)
    • Moves into cell down concentration gradient
  • Facilitated diffusion glucose transporter (GLUT)
    • Moves down concentration gradient into interstitial fluid
• Sodium-Potassium-ATPase pump activity maintains the low Sodium concentration in cell
• There is a linear proportionality of the filtered load related to plasma concentration
• Line shows variation with plasma [glucose]
• Excreted products follow the formula Filtered - reabsorbed, and shows renal threshold at 200 mg/dl

Amino Acids

• Reabsorbed in the proximal tubule (PT)
• Consists At least 8 amino acid transporters with 6 Sodium-dependent transporters
• Transporters show an Overlapping amino acid specificity
• Filtered PROTEIN is reabsorbed in PCT by endocytosis and degraded to amino acids
• Inactivation of small polypeptide hormones e.g. insulin.

PCT Reabsorption summary

• Sodium coupled transporters for:
  • Glucose
  • Amino acids
• Passive reabsorption:
  • Urea
  • Chloride
  • Potassium
• Bicarbonate can be processed in a way that links to the body's acid base balance.

Tubular secretion Processes

• Happens in the Proximal tubule & is a two stage process
• Involves basolateral and luminal (brush border) membrane transporters
• Transporters are broadly selective
• Only way to process some protein bound molecules

Secretion of Anions and Cations

• Organic acids (anions) are secreted in the proximal tubule
  • Endogenous molecules, e.g. bile salts
  • Exogenous molecules, e.g. penicillin
  • Diagnostic agent, e.g. para-aminohippuric acid (PAH).

Example Actions of Organic Anion in Proximal Tubule

• Organic anion (OA-) enters epithelial cell via organic anion counter transporters
• OA- enters tubule lumen via ATP-dependent primary active transporters
• Organic bases (cations) are secreted in proximal tubule:
  • Endogenous molecules, e.g. creatinine
  • Exogenous molecules, e.g. morphine
• Organic cations (OC) enter proximal tubule cell via facilitated diffusion transporters.
• Organic cations enter tubule lumen via counter-transporters.

Renal system hormone related glossary

• Hormones are divided into those acting on the kidney and produced by the kidney

Hormones that act on the kidney

• ADH peptide released by the posterior pituitary which water reabsorption in collecting duct
• Aldosterone steroid hormone produced by the adrenal cortex that promotes sodium reabsorption in the collecting ducts
• Natriuretic peptides are produced by cardiac cells that promote sodium excretion in the collecting ducts

Hormones produced by the kidney

• Renin protein released by the juxtaglomerular apparatus that results in the formation of angiotensin II
• Angiotensin II acts directly on the proximal tubules and, via aldosterone, on the distal tubules to promote sodium retention
• It is also a potent vasoconstrictor.
• Flow is equal to pressure difference over resistance
• Resistance is equal to (8 * vessel length * blood viscocity) / (pie * radius of vessel lumen^4)