Renal Flashcards
What are the functions of the kidney
Filtration of the blood Production of urine Reabsorption of filtered substances Excretion of metabolic waste and xenobiotics Water and acid-base balance Production of glucose (gluconeogenesis) Endocrine functions
What hormones are produced by the kidneys ?
Calcitorol - stimulated by PTH in response to hypocalcemia (increase reabsorption)
Renin- BP regulator (increase H2O reabsorption)
Erythropoietin - erythropoiesis
What is the functional unit of the kidney?
Nephron
What are the two types of nephrons?
Cortical nephrons - short loops supplied by peritubular capillaries
Juxamedullary nephrons- cortex and medulla supplied by vasa recta (essential for urine concentration)
What is the Malpighian body?
The glomerulus surrounded by the Bowmans capsule.
Trace filtrate flow through the nephron and the main function of that part of the nephron.
Malpighan body- glomerulus and bowmans capsule-> production of primary ruin through filtration
Proximal convoluted tubule- reabsorption of solute and water, excretion of drugs
Loop of Henule - thick and thin descending limb, and ascending limb (only in juxtamedullary nephrons have thin acceding limbs)
Urine concentration
Distal convoluted tubule- reabsorption of solutes
Collecting duct - water balance
What is the sequence of renal blood supply ?
Abdominal aorta -> renal artery -> interlobar arteries ->arcuate artery -> interlobular arteries (into renal capsule) -> afferent arterioles -> globular capillaries -> efferent arterioles -> peritubular capillaries / vasa recta
Why is urine production a highly energy consuming process?
Active transport of solutes across membranes
ATP-dependant transport
What are examples of renal IR?
Organ transplants
Cardiac and vascular surgeries
Acute renal failure
Toxins
Renal ischemia has what affect on the kidney?
Inflammatory response to O2 deprivation
-> production of ROS -> damage DNA, Lipids, and proteins => Loss of cell polarization => Apoptosis
Impaired renal function
What is the regenerative capacity of the kidney?
Nephrons cannot be replaces but tubular cells have some regenerative capacity
Migration and proliferation of surrounding cells to mesechymatic phenotype
What is the glomerulus?
Compact network of capillaries that retains cellular components and proteins
What is the glomerular filtration rate dependent on?
Renal plasma flow (RPF) - rate the kidney is perfused with blood
What percentage of blood plasma is filtered through the glomeruli?
20% is filtered
99% of this filtrate is reabsorbed
Epithelial cells covering the glomerulus?
Podocytes
What are the components of the filtration barrier?
Capillary endothelium (fenestrated) Glomerular basement membrane (glycoproteins) Visceral epithelium (podocytes)
What are the three layers of the glomerular basement membrane?
Lamina rara interna
Lamina densa
Lamina rara externa
What is the lamina densa made up of?
Glycoproteins (laminins, type IV collagens, proteoglycans)
Impermeable to proteins
Filterability of substances is dependent on what factors?
Size (radius and molecular weight)
Electrical charge - negative charged large molecules are filtered less easily than positively (cationic) charged molecules of the same molecular size
Plasma protein binding
What is the main driving force for filtration
Hydrostatic pressure
Oncotic pressure of blood plasma opposes the hydrostatic pressure
How does the pressure of the glomerular capillaries change over the length of the glomerulus?
Hydrostatic is relatively constant
Oncotic pressure increases gradually along the length
What are methods used to determine renal function?
Urine strips - proteins Centrifuge + microscope -crystals Refractometer -concentration/SG Protein detection tests Urine concentration test Clearance
What properties does an indicator substance for GRF have?
Freely filterable
Amount filtered must not change due to restoration/secretion in the tubule
Must not be metabolized in the kidney
Must not alter renal function
What is renal clearance ?
Clearance = GFR
Rate the plasma is cleared of a substance if the substance is freely filterable
How is blood flow regulated in the kidney ?
Auto regulatory window between 80-180mmHg
Myogenic reflex
RAAS
Tubuloglomerular feedback
Where is renin produced?
Wall of the cells of afferent arterioles
What is the myogenic reflex (Baylis effect) ?
Detects changes in glomerular perfusion
Increase tension of arteriolar wall -> depolarization of vascular smooth muscle -> Ca2+ enters cell -> muscle cell contraction -> constriction of afferent arteriole
What is the tubulogomerular feedback mechanism?
Increase GFR -> increased tubular fluid -> NaCL in macula densa -> depolarization of cells and ATP release -> suppression of renin release from juxtaglomerular cells -> mesangial cells contraction increase resistance of afferent arteriole -> reduced GFR
Describe the RAAS?
Decreased arterial presssure -> kidney releases renin-> coverts antiogentinogen to angiotensin I -> ACE coverts angiotensin I to angiotensin II-> increase water retention -» increase BP
What affect does the sympathetic system have on renin?
B-adrenergic stimulation induces renin release
What are vasodilator agents ?
NO (NOS)
PGE2- modulate mesagnial cell contraction
Counteract constriction to maintain oxygenation
What are constricting factors
Endothelin,
TXA2
ANG2
B-adrenergic stimulation
What is primary urine?
Ultrafiltrate in the Bowmans capsule space (same concentration of solutes as plasma)
How can you determine rental tubule function?
Fractional excretion rate - net rate of reabsorption and secretion of a filtered substance
FEx = Ux/Px / Ucre/Pcre
Describe cells of the proximal tubule ?
Polarized (apical and basolateral membrane)
Brush borders (microvilli)
Tight junctions
By what two ways can tubule fluid components be moved back into the blood?
Transcellular pathway- carrier mediated across basolateral and apical
Paracellular pathway - through tight junctions (passive diffusion/ solvent drag)
Primary active transport
Fueled directly by ATP consumption
Eg Na/K ATPase to establish Na gradient
Secondary Active transport
Driven by the electrochemical gradient produced by the primary active transporter (eg Na cotransporter)
Tertiary active transport
Carrier is driven by the gradient generated by a secondary active transport
H+ gradient can be used to move a third substance like tri and dipeptides into the cell
Secondary transport systems are important for what substances?
Glucose, amino acid, prostate, sulfate, and citrate
How are peptides reabsorbed in the kidney?
Tertiary active transport -di and tripeptides
H+ gradient
Oligopeptides are hydrolyzed by extracellular peptidaes
Na symporter -> secondary active transport
How are low molecular weight proteins reabsorbed int the kidney?
Receptor-mediated endocytosis
Protein binds to receptor -> endocytosis -> fusion with lysosomes and degraded -> vesicle recycled back to plasma membrane
Saturation of these receptors -> unrecovered proteins -> proteinuria
How can proteinuria be classified?
Pre-renal - concentration freely filterable proteins in blood is increased
Intrarenal -glomerular filter is damaged
Post-renal- tubular loss of protein (inflammatory process)
Where and how is bicarbonate reabsorbed in the kidney??
Proximal tubule
Sodium gradient drives Na/ H transporter. H+ out to tubular lumen and combines with HCO3 to form Co2
Co2 enters cell through aquaporins and is covered back to HCO3 by carbonic anhydrase
How is chloride ion reabsorbed in the proximal tubule?
Paracellular
How is calcium reabsorbed in the proximal tubule?
Uptake by paracellular and solvent drag
What substances are secreted into the proximal tubule?
Organic ions (endogenous or exogenous) -if protein bound-> poorly filtered
How are organic ions secreted?
Basolateral uptake and apical secretion (carrier mediated)
What proteins are involved in organic anion secretion and where are they located on the PT?
Organic anion transporter ( OAT) - basolateral
Multrdrug Resistance Protein 2 (MRD2) -apical and linked with ATP
What proteins are involved in secretion of organic cations and where are they located on the PT?
Organic cation transporter (OCT) - basolateral
Multidrug resistance - (MDR1) - apical and linked with ATP
How is glucose reabsorbed and where?
Sodium-dependent transporter (SGLT) -secondary active transport
In the proximal tubule
High levels of plasma glucose (>10-15mmol) has what effect on reabsorption of glucose?
Carriers become saturated -> excess glucose secreted in urine.
Glucose is osmostically active so it pulls water with it => polyuria
What are the segments of the loop of Henule?
Thick descending limb ( sometimes concidered part of PT)
Thin descending limb
Thin ascending limb ( not present in cortical nephrons)
Thick ascending limb
What type of nephrons are especially important for urine concentration
Juxtamedullary ( long loops) nephrons
The thin descending limb is highly permeable to ________ and has reduced permeability to __________.
What is the overall effect of this?
Water (aquaproins on apical membrane)
Sodium, chloride, and urea
Tubular fluid becomes more concentrated (increased osmolality)
The ascending limbs are impermeable to _____________. The thick ascending limb reabsorbed high amounts of _________.
What is the net effect of this?
Water.
Solutes (sodium, chloride, potassium, calcium, bicarbonate, magnesium)
Dilution of tubular fluid .
The descending limb ________ tubular fluid and the ascending limbs ________ tubular fluid
Concentrate
Dilute
What is the most significant transport system in the thick ascending limb?
Na, K Cl cotransporter (NKCC) - move solutes from the lumen back to interstitium
How are Ca, Mg and Na reabsorbed from the ascending limb?
Paracellular - lumen is positively charged, forces ions to move back to interstitium
What is the main process in the distal convoluted tubule?
Reabsorption of solutes Ca channels (TRPV)-apical Na/Cl cotransporter (NCC)-apical K channels-basolateral Ca/Na exchanger (NCX)- basolateral
What is the main function of the late DT and cortical collecting duct?
Water reabsorption through aquaporins
What is the main process in the inner medullary collecting ducts?
Urea reabsorption - urea transporters
What are the two types of cells in the collecting duct?
Principal cells and intercalated cells
What are the important transport systems of the CD principal cells?
NaCl reabsorption by ENaC
K secretion by ROMK
Type A intercalated cells secretes _____ and reabsorbs _______
H+
HCO3-
Type B intercalated cells secrete _____ and reabsorb _______
HCO3-
H+
What effect does PTH have on transporters in the kidney?
Inhibits apical NaPi transporters (phosphate not reabsorbed)
Stimulates apical uptake of Ca2+
Vitamin D hormone synthesis in the kidney -> increased Ca reabsorption from intestines
What hormones stimulate solute reabsorption in the kidney?
Antigotensin II
Aldosterone
ADH
Work on transporters
What hormones inhibit solute reabsorption in the kidney?
NO
Endothelin -1
ANP
Inhibiting sodium transporters
How does ANP inhibit solute reabsorption?
Inhibit aldosterone and renin release
Increase Na+ excretion
