Kidney function I: Filtration, Reabsorption and Secretion Flashcards
Functions of kidney
-Excretion of metabolites or ingested substances
-Control of body fluid composition
-Endocrine
Examples of metabolites/substances kidney excretes
-Urea from protein catabolism
-Uric acid from nucleic acid breakdown
-Creatinine from muscle creatine
-Hormone metabolites e.g. growth hormone
-End products of haemoglobin breakdown
-Foreign chemicals: drugs, pesticides
Examples of kidney control of body fluid composition
-Volume regulation - linked to sodium concentration
-Osmoregulation - water balance
-pH regulation
Endocrine function of kidneys
Hormones that act on kidneys:
-ADH
-Aldosterone
-Natriuretic peptides
-Parathyroid hormone
-Fibroblast growth factor 23
Hormones produced by kidney:
-Renin
-Activated vitamin D3
-Erythropoietin
-Prostaglandins
Gross structure of kidney
Microanatomy of kidney
-Each kidney contains >1 million nephrons
-Each nephron contains renal corpuscle and tubule
Simplified diagram of renal corpuscle
Filtration interface in renal corpuscle
Learn stuff in brackets
Breakdown of the nephron
2 types of nephron
Cortical (85%)
-outer 2/3 of cortex
-short Loop of Henle
Juxtamedullary (15%)
-inner 1/3 of cortex
-long Loop of Henle
-produces concentrated urine
Where are renal corpuscles of nephrons found?
-Outer cortex region of kidney
What makes up juxtaglomerular apparatus?
-Juxtaglomerular cells -release renin
-Macula densa
The nephron blood supply
-Peritubular capillaries found close to tubule of nephron
-Peritubular capillaries in Loop of Henle are the Vasa Recta
-2 sets of arterioles (afferent and efferent)
-2 sets of capillary beds (glomeruli and peritubular)
Basic renal processes
-Glomerular filtration
-Tubular secretion
-Tubular reabsorption
-Metabolism (e.g. glutamine)
Glomerular filtration
-Movement of fluid and solutes from glomerular capillaries into Bowman’s space
-20% of the plasma that enters the glomerulus is filtered and enters the Bowman’s space
Tubular secretion
-The secretion of solutes from the peritubular capillaries into the tubules
-Occurs in proximal tubule and collecting duct
Tubular reabsorption
-The movement of materials from the filtrate in the tubules into the peritubular capillaries
-Mainly occurs in proximal tubule
Amount of substance excreted in urine = amount filtered + amount secreted - amount reabsorbed
What does filtration of substances depend on?
-Molecular size
-Charge
-Possibly shape
-Most plasma constituents are freely filtered - except proteins
Under what molecular mass are substances freely filtered in the glomerulus
7000 Daltons
How does molecular charge affect how freely they are filtered?
-Fixed sited of negative charges will:
-repel negatively charged dextrans
-encourage the filtration of positively charged dextrans
Composition of ultrafiltrate
-Cells and large proteins not filtered across barrier
-Certain drugs and ions bind to proteins so are not filtered
E.g.
-Acidic drugs can bind to protein, albumin
-Basic drugs can bind to a1-acid glycoprotein
-40% of plasma Ca is bound to proteins, therefore only 60% can be freely filtered
What can infection, damage to glomerulus, hypertension result in?
-Protein in urine (proteinuria)
-Hb in urine (hameoglobinuria)
-Red cells in urine (haematuria)
GFR definition
-Volume of fluid filtered from the glomeruli per minute (ml/min)
-Higher GFR, means greater excretion of salt and water
-Regulated by neural and hormonal input
What does GFR depend on?
1) Net filtration pressure of Starling’s forces
2) Permeability characteristics of filtration interface
3) Surface area of filtration interface
What factors affect Starling’s forces involved in filtration
1) Hydrostatic pressure difference
=> Plasma will flow from high to low
2)Colloid osmotic pressure difference
=> Plasma will flow from a low to high
Net glomerular filtration pressure calculation
How does blood flow affect GFR?
-Constricting afferent arteriole, reduces hydrostatic pressure, reducing GFR
-Dilating afferent arteriole, increases hydrostatic pressure, increasing GFR
Which is more permeable? Glomerular capillaries or peritubular capillaries?
Glomerular capillaries
How does surface area affect GFR?
-Intraglomerular mesangial cells contain smooth muscle actin
-Sympathetic stimulation causes smooth muscle to contract
-This reduces surface area for filtration
Structure of proximal tubule (cross section)
-Capillary walls are endothelial cells
-Proximal tubule is epithelial cells
Proximal tubule wall structure
-Walls are a single layer of columnar cells
What 3 things help proximal reabsorption of organic nutrients (e.g. glucose and amino acids)
-Na-coupled co-transporter
-Tubular maximum (Tm) system
-Specific transporters
How is glucose reabsorbed?
Na+ dependent glucose co-transporter (SGLT)
-Na+ moves into cell down concentration gradient and provides energy fro glucose to move against concentration gradient
Facilitated diffusion glucose transporter (GLUT)
-Glucose moves down concentration into interstitial fluid
-Low Na+ concentration in cell maintained by Na+/K+ ATPase pump activity
Where and how are amino acids reabsorbed?
-Proximal tubule
-Different transporters for different groups of amino acids
-Transporters for positively charged (basic) amino acids
-At least 8 amino acid transporters
-6 are Na+-dependent
Where and how are proteins reabsorbed?
-Vast majority of filtered protein reabsorbed in PCT by endocytosis
-Important for inactivation of small polypeptide hormones (e.g. insulin and growth hormone)
Summary of PCT reabsorption
Na coupled transporters for:
-glucose
-amino acids
-phosphate
-sulphate
Passive reabsorption
-Urea
-Chloride
-Potassium
-Calcium
Bicarbonate
-Related to H+ secretion
-Important in acid-base balance
Secretion in proximal tubule
-Two stage process
-Involves basolateral and luminal membrane transporters
-Transporters broadly selective
-Only means of excretion for some protein bound molecules
Which organic acids (anions) are secreted in the proximal tubule?
Endogenous molecules:
-bile salts
-fatty acids
-prostaglandins
Drugs:
-Penicillin
-Furosemide
Diagnostic agent:
-Para-aminohippuric acid (PAH)
