Renal Flashcards
What do you call the maintenance of the internal environment compatible with life?
Homeostasis
What is the net gain of water per day?
Zero: Fluid gained per day = fluid lost per day
Which organ system contributes to homeostasis by adjusting water and electrolyte levels?
Renal System: mainly by producing urine
What is urine?
Urine is an ultrafiltrate of blood
Waste product from Proteins
Urea
Waste product from Purines
Uric Acid
Waste product from Muscles
Creatinine
Waste product from RBCs
Bilirubin
Excretion of variable amounts of water and sodium; Involved in RAAS
Blood pressure regulation
Excretion of excess acids and bases
Regulation of Acid- Base balance
Increases RBC production in response to hypoxia
Production of Erythropoeitin (EPO)
Produces glucose during the starvation state
Gluconeogenesis
Location of Kidney
T12-L3
Weight of Kidney
150g
Highly-fenestrated, responsible for GFR
Glomerular Capillaries
Supplies O2 & glucose to the tubular cells
Peritubular Capillaries
Secretes Erythropoietin (EPO)
Interstitial Cells
Hairpin loop-shaped peritubular capillaries of the juxtaglomerular nephrons that participate in countercurrent exchange
Vasa Recta
Capacity of the Urinary Bladder
600ml
Urge to urinate
150ml
Reflex contraction of the Urinary Bladder
300ml
Bladder muscle
Detrusor muscle
Internal Urethral Sphincter
Involuntary
External Urethral Sphincter
Voluntary
Functional and Structural Unit of Kidney
Nephron
of Nephrons per kidney
1 million
75% of nephrons
Cortical Nephrons
25% of nephrons
Juxtamedullary Nephrons
Location of Cortical Nephrons
Renal Cortex
Location of Juxtamedullary Nephrons
Corticomedullary Junction
Loops of Cortical Nephrons
Short
Loops of Juxtamedullary Nephrons
Long
Capillary Network of Cortical Nephrons
Peritubular Capillaries
Capillary Network of Juxtamedullary Nephrons
Vasa Recta
The only capillaries in the body which drain into arterioles
Glomerular Capillaries
50x more permeable than skeletal muscle capillaries; Highly fenestrated with pores 8 nanometer in diameter
Capillary Endothelium
Capillary endothelium secretes:
Nitric Oxide & Endothelin-1
Have large spaces; With Type IV Collagen, Lainin, Agrin, Perlecan, Fibronectin
Basement Membrane
Found in between capillaries; Contractile, mediates filtration, take up immune complexes; Involved in Glomerular Diseases
Mesangial Cells
Cells of capillary endothelium
Podocytes
Parts of Podocytes
Foot processes Filtration slits with filtration slit diaphragm
Filtration Slit Diaphragm is made up of:
NephrinNEPH-1PodocinAlpha-actinin 4CD2-AP
“Glomerular cells of the Afferent Arterioles”; At the walls of Afferent Arterioles; Secrete Renin
JG Cells
Found in the walls of the Distal Convoluted Tubule; Monitor Na+ concentration in the DT (and consequently, blood pressure)
Macula Densa
“Visceral Epithelium” of the kidney
Podocytes
“Parietal Epithelium” of the kidney
Bowman’s capsule
What are the filtration and charge barriers?
EndotheliumBasement membraneFoot processes of Podocytes
What is the charge of this charge barrier and what does it block?
NegativePrevents filtration of albumin and other negatively-charged proteins
Movement from Glomerular Capillaries to Bowman’s space
(Glomerular) Filtration
Movement from tubules to interstitium to peritubular capillaries
(Tubular) Reabsorption
Movement from peritubular capillaries to interstitium to tubules
(Tubular) Secretion
(Amount Filtered) - (Amount Reabsorbed) + (Amount Secreted)
Excretion
Amount filtered in the glomerular capillaries per unit time
GFR
Normal GFR
125ml/min or 180L/day
GFR/RPF
Filtration fraction
Filtered freely
20 angstrom or less
Not filtered at all
> 42 angstrom
Afferent Arteriole Dilatation
GFR increases
Afferent Arteriole Constriction
GFR decreases
Efferent Arteriole Dilation
GFR decreases
Efferent Arteriole Constriction (moderate)
GFR increases
Efferent Arteriole Constriction (severe)
GFR decreases
Increased GC Hydrostatic pressure
GFR increases
Increased GC Oncotic pressure
GFR decreases
Increased BS Hydrostatic pressure
GFR decreases
Increased Kf
GFR increases
What are the causes of decreased Kf?
Renal Diseases DMHPN
What is the cause of increased BS hydrostatic pressure?
Urinary Tract Obstruction
What are the causes of decreased GC hydrostatic pressure?
Hypotension (Decreased arterial pressure)ACE-I (Decreased efferent arteriole constriction)Sympathetic Activity (Increased afferent arteriole constriction)
What are the hormones that will increase GFR?
EDFRPGE2PGI2BradykininGlucocorticoidsANPBNP
Which hormone will preserve GFR?
Angiotensin II (preferentially constricts efferent arteriole)
Which hormone will increase Renal Blood Flow (RBF)?
HistamineDopamineANPBNP
What is one possible effect of ACE-I in a patient with HPN secondary to Renal Artery Stenosis?
Renal Failure
(Renal Artery Pressure-Renal Vein Pressure) / Total Renal Vascular Resistance; Exhibits local autoregulation at BP between 75-160mmHg
Renal Blood Flow
What do you call massive sympathetic stimulation that results in massive vasoconstriction of the kidneys?
CNS Ischemic Response
“Constant sodium load delivered to distal tubule”; Primary Mechanism for Autoregulation of GFR
Tubuloglomerular Feedback
Vasoconstricts afferent arteriole
Adenosine
Vasodilates afferent arterioles
Nitric Oxide
“Percentage of solute reabsorbed is held constant”; Buffers effects of drastic GFR changes in urine output
Glomerulotubular Balance
Substance start to appear in the urine; Some nephrons exhibit saturation
Renal Threshold
All excess substance appear in the urine; All nephrons exhibit saturation
Renal Transport Maximum
Does not have Transport Maximum and Threshold
Gradient-time Transport
Gradient-time Transport: Rate of transport is dependent upon:
Electrochemical gradientMembrane permeabilityTime
“Workhorse of the Nephron”; With low columnar with extensive brush border (microvilli)
Proximal Convoluted Tubule
Reabsorption in Proximal Convoluted Tubule
100% filtered Glucose and Amino Acids66% NaCl and water
Secretion in Proximal Convoluted Tubule
H+, organic acids, bases (Rapidly filtered and almost none reabsorbed)
Which is more hypertonic relative to the other - fluid entering the PCT or fluid leaving the PCT?
None (isoosmotic reabsorption takes place)
Thin segment lining of Loop of Henle
Simple squamous with no brush border and few mitochondria
Thick segment lining of Loop of Henle
Simple cuboidal
With graded osmolarity; Constant: 20% filtered water is reabsorbed and 25% Na, K, Cl is reabsorbed; H is secreted via Na-H countertransport
Loop of Henle
Impermeable to solutes; Permeable to water
Descending Limb of Loop of Henle
Impermeable to water; Permeable to solutes
Ascending Limb of Loop of Henle
Contains juxtaglomerular apparatus, macula densa, juxtaglomerular cells (JG Cells), Lacis cells; Similar characteristics to thick segment of LH (relatively impermeable to water)
Early Distal Tubule (1st Part of the Distal Tubule)
Contains principal cells, intercalated cells; Responsive to effects of Aldosterone
Late Distal Tubule (2nd Part of the Distal Tubule)
Absorb Na (using ENaC channels) water and Secrete K
Principal Cells
Absorb K and Secrete H
Intercalated Cells
Where K sparing diuretics acts
ENaC Channels
Site of regulation of final urine volume and concentration; Responsive to Vasopressin
Collecting Duct
Maximum urine osmolality
1200mosm/L
Minimum Urine Volume
500ml
Increased by increased BP; Decreased by Afferent or Efferent Arteriole vasoconstriction
Peritubular Capillary Hydrostatic Pressure
Increased by Plasma protein concentration and Filtration fraction
Peritubular Capillary Oncotic Pressure
What happens to tubular reabsorption when Peritubular Capillary Hydrostatic Pressure increases?
Decreases
What happens to tubular secretion when Peritubular Capillary Hydrostatic Pressure increases?
Increases
What happens to tubular reabsorption when Peritubular Capillary Oncotic Pressure increases?
Increases
What happens to tubular secretion when Peritubular Capillary Oncotic Pressure increases?
Decreases
Site of Action of Aldosterone
Distal Tubule
Site of Action of Angiotensin II
PCTTALLHDT
Site of Action of Catecholamines
PCT TALLHDT/CD
Site of Action of Vasopressin
DTCD
Site of Action of ANP/BNP
DTCD
Site of Action of Uroguanylin, Guanylin
PCTCD
Site of Action of Dopamine
PCT
Site of Action of PTH
PCTTALLH
Effects of Aldosterone
Increase Na, water reabsorptionIncrease K, H secretion
Effects of Angiotensin II
Increase Na and water reabsorption
Effects of Catecholamines
Increase Na, water reabsorption
Effects of Vasopressin
Increase water permeability and reabsorption
Effects of ANP and BNP
Decrease Na reabsorption
Effects of Uroguanylin and Guanylin
Decrease Na, water reabsorption
Effects of Dopamine
Decrease Na, water reabsorption
Effects of PTH
Decrease Phosphate reabsorptionIncrease Ca reabsorptionStimulates 1 Alpha Hydroxylase
What are the triggers for ADH secretion?
Increased Plasma OsmolarityDecreased Blood PressureDecreased Blood Volume
What is the effect of alcohol on ADH secretion?
Alcohol decreases ADH secretion
Which hormone secreted by DT and CD acts similar to ANP?
Urodilatin
Rate at which substances are removed (cleared) from plasma in the kidneys
Renal Clearance
If a substance has a high clearance, what are the blood and urine level of this substance?
Low Blood levelHigh Urine level
If a substance has a low clearance, what are the blood and urine level of this substance?
High Blood levelLow Blood level
Which substance has the highest clearance?
Para-Amino Hippuric Acid (PAH)
Which substances have the zero clearance?
Glucose, Amino Acids
Which substances have a clearance that can be used to estimate GFR?
Inulin, Creatinine (BUN and Creatinine serum concentration may also be used)
Which substances have a clearance that can be used to estimate Renal Blood Flow and Renal Plasma Flow?
Para-Amino Hippuric Acid (PAH)
Substances that do not appear in the urine have a clearance of
Zero
Substances filtered and partially reabsorbed have a clearance ? Than the GFR
Less
Substances filtered and with net secretion have a clearance ? Than the GFR
More
Clearance of Inulin is ? To that of the GFR
Equal
How many liters of fluid per day passes thru the kidneys?
180L of fluid/day
Percentage of filtered water that is reabsorbed
87-98.7%
Plays major role in water reabsorption
Vasopressin and ADH
Threshold of Glucose
200mg/100ml
Maximum of Glucose
375mg/100ml
Region between threshold and maximum
Splay
Glucose transport from the lumen to PCT
SGLT-2 (Secondary Active Transport)
Glucose transport form the PCT to the Peritubular Capillaries?
GLUT-1 and GLUT-2 (facilitated diffusion)
Major role in electrolyte balance
Na
Na is actively transported in all parts of the renal tubule EXCEPT
Descending limb of Loop of Henle
Plasma K
4.2mEq/L
Can cause Arrhythmias
HyperkalemiaHypercalcemia
Can cause weakness
Hypokalemia
First line of defense
Movement of K across ECF to ICF
Factors that shift K into cells
InsulinAldosteroneB-Adrenergic StimulationAlkalosis
Factors that shift K out of cells
Insulin DeficiencyAddison’s DiseaseB-Adrenergic BlockadeAcidosisCell lysisStrenuous ExerciseIncrease ECF Osmolarity
Increased Plasma K increases secretion via
Principal Cells
Decreased Plasma K increases reabsorption via
Intercalated Cells
Causes of Increased K secretion
High K doetHyperaldosteronismAlkalosisThiazide diureticsLoop diureticsLuminal anions
Causes of decreased K secretion
Low K dietHypoaldosteronismAcidosisK sparing diuretics
Plasma Ca
2.4mEq/L
Can cause Tetany
Hypocalcemia
Less calcium bound to plasma proteins
Hypercalcemia (Acidosis)
More calcium bound to plasma proteins
Hypocalcemia (Alkalosis)
Factors that alter renal calcium excretion: Decreased excretion
Increased PTH, Plasma PhosphateDecreased ECF, BPMetabolic AcidosisVit D3
Factors that alter renal calcium excretion: Increased excretion
Increased ECF, BPDecreased PTH, Plasma PhosphateMetabolic Alkalosis
Trio of Electrolytes: High H levels
HypercalcemiaHyperkalemia
Transport maximum of phosphate
0.1mM/min
Plasma Mg
1.8mEq/L
Magnesium stored in the bones
50%
Plasma Mg excreted daily
10%
Percentage of water reabsorbed automatically before the collecting duct
87%
If ADH levels are high, what happens to water reabsorption at the collecting duct?
High (more aquaporins inserted)
If ADH levels are high, what happens to urine volume at the collecting duct?
Low (min:500ml/day)
If ADH levels are high, what happens to urine concentration at the collecting duct?
High (max:1200mOsm/L)
If ADH levels are low, what happens to water reabsorption at the collecting duct?
Low (less aquaporins inserted)
If ADH levels are low, what happens to urine volume at the collecting duct?
High (max:20L/day)
If ADH levels are low, what happens to urine concentration at the collecting duct?
Low (min:50mOsm/L)
Provides the stimulus for water reabsorption
Countercurrent Mechanism
Provides the opportunity for water reabsorption
ADH
Countercurrent Multipliers
Loop of Henle
Creates the Corticopapillary Osmotic Gradient in the Renal Interstitium
Countercurrent Multipliers
Countercurrent Exchangers
Vasa Recta
Maintains the Cirticopapillary Osmotic Gradient in the Renal Interstitium (prevents dissipation of gradient)
Countercurrent Exchangers
Why is the Loop of Henle able to act as a countercurrent multiplier?
Countercurrent Flow (hairpin-loop shape)Difference in permeability to water and electrolytes in the Ascending and Descending WallNa-K-2Cl pump in the TAL LHSlow Flow in the LH
What is the end result due to the countercurrent mechanism?
Corticopapillary Osmotic Gradient: 300mOsm/L as you enter the PCT, 1200mOsm/L at the tip of LH
Why do you need a countercurrent exchanger?
Gradient would dissipate quickly if Na and Urea are removed quicklyVasa Recta preserves this gradient basically by “rotating” Na, water and urea
Contributes to the hyperosmolarity of the renal medulla
Urea Recycling
Percentage of Renal Medullary Interstitial Osmolarity
50%
Stimulated by ADH
Urea Receptors (UT-1)
Osmolarity at the tip of LH
600-1200mOsm
True or False: More urea reabsorbed, the more concentrated the renal interstitium becomes, the more concentrated the final urine is
True
Found in the Anteroventral eall of 3rd Ventricle & Preoptic Nuclei
Thirst Center
Control of Thirst: Increased thirst
Increase Osmolarity, AngiotensinDecrease Blood Volume, BPDryness of mouth
Control of Thirst: Decreased thirst
Increased Blood Volume, BPDecreased Osmolarity, Angiotensin IIGastric Distention
Found in the pons
Micturition Center
Micturition Center can be inhibited by
Cerebral Cortex
Normal Plasma H
0.00004mEq/L
Normal Plasma pH
7.4
Systems that regulate H concentrations
Body Fluid Buffer SystemsRespiratory CenterKidneys
Mechanisms of Renal Regulation of Acid-Base Balance
Secretion of HReabsorption of filtered HCO3Production of new HCO3
Due to Decreased Ventilation
Respiratory Acidosis
Due to Increased Ventilation
Respiratory Alkalosis
Due to excess acid or loss of base
Metabolic Acidosis
Due to loss of acid or gain of base
Metabolic Alkalosis
Decreased HCO3; Increased Organic Anions to maintain electroneutrality
High Anion Gap Metabolic Acidosis (HAGMA)
Decreased HCO3; Increased Chloride to maintain electroneutrality; Also called Hyperchloremic Metabolic Acidosis with Normal Anion Gap
Normal Anion Gap Metabolic Acidosis (NAGMA)