MSAP Renal Physiology Notes Flashcards
Basic Functions of the kidneys
Functions:
Excretory (producing urine), regulatory (controlling BP and filtering/cleaning the blood), and endocrine (synthesizing and secreting hormones)
- The body’s “washing” machine
- Total renal blood flow about 25% of cardiac output (1800 L/day or 1.25 L/min)
- Filters about 180L/day; reabsorbs >99% of plasma ultra filtrate to make urine
Nephron
Nephron is the functional unit of the kidney (millions)
Urine is formed in the nephron–> urine drains in the minor calyces–>major calyces–> renal pelvis–> ureter
Proximal and Distal convoluted areas are in the cortical area
Loop of henle in the medullary area
More than one nephron is able to dump into one collecting duct
Juxtamedullary Nephron
Dilute and concentrate urine; more important for urine production
Bowman’s capsule is closer to medullary border
Extend fully into inner medullary area
All three areas of the loop of henle (descending, thin ascending, thick ascending)
Cortical Nephron
more common
Bowman’s capsule is higher up in the cortex
No thin ascending limp
Unable to fully dilute/ filter urine
Nephron associated vasculature
Afferent artery: from renal artery to the golumeral capillaries (network that is responsible for filtration)
Efferent artery: carries blood away from glomerular capillaries ; becomes the peritubular capillary network after is starts to wrap around the proximal and distal convoluted tubules (blood supply for the cortical portion of the nephron)
Vasa Recta- capillaries close to the Juxtamedullary nephrons only (hairpins close to think/thick ascending and thin descending limps of loop of Henle)
Filtration (factors that affect filtration)
2 components determine flux across glomerulus: 1) permeability and 2) glomerular filtration pressure
- Permeability: a) Size (small molecules with radii <15 A able to freely filtrate (Mg, Cl, Water, glucose, etc.) b) 15-35 A: inverse relationship with size and filterability (smaller size= easier filterability) c) Large nodules (greater than 35 A) no filterability at all
- Charge (15-35A: Cations>neutral>anions) (Remember pedicels are negatively charged!)
Freely filtered molecules
passes readily through barrier into bowman’s space; [plasma]= [Bowman’s space]
Non-freely filtered molecules
Does not pass freely through the barrrier into the bowman’s space
[plasma]> [Bowman’s space]
Filterability of 1= freely filtered; less than 1 means less filterable
Filtration barriers that impede movement of water and various solutes
- Basement membrane is major barrier with endothelium in intimate contact with glomerular capillaries
- Epithelial layer of Bowman’s capsule has specialized cells (podocytes) that form many extensions that look like feet (pedicels) (pedicle surface is negatively charged)–> Pedicles interdigitate forming filtration slits
Filtration barriers that impede movement of water and various solutes
Starling’s Forces
Starling Forces: x4 pressures affecting fluid across capillary wall
2 hydrostatic pressure pushes H2O away (out capillary/interstituim)
2 oncotic pressures: proteins drawing H2O towards them (into the capillary/interstituim)
Hydrostatic Pressures
- Hydrostatic pressure of Capillary (PGc): favors filtration; force that preventss water from entering the capillary
- Hydrostatic pressure of intersttium (PBS): opposes filtration/favors reabsorption (H2O follows solutes- increase pressure- forces H2O into capillary)
Oncotic Pressures
- _Oncotic pressure of blood (plasma) (_πGC )- opposes filtration/favors reabsorption; major driving force in reabsorption (high concentration of proteins from differnet arterioles)
- Oncotic pressure of interstitial fluid/Bowman’s space (__πBS): favors filtration (+)- no proteins in bowman’s space (0 mmHg)
Net force pressure
ΔP= (factors that favor filtration)- (factors that favor reabsorption)
ΔP= (PGC+ πBS) – (PBS+πGC) (have to use this version if oncotic pressure of bowman’s space is provided)
πBS= Oncotic pressure of bowman’s space= usually zero or negligible
ΔP= PGC- PBS- πGC (able to use this version of the equation if the oncotic pressure is negligible
PGC= 45 mmHg (somewhat constant; usually around 45-60mmHg)
PBS= 10 mmgHg (pretty constant as well usually about 10mmHg)
Clinical Situation__: If a kidney stone blocked a renal calyx, how would this affect filtration pressure in the nephrons emptying into it?
Answer: The fluid is going to backup in the nephron; increase in hydrostatic pressure; can back up to the point that there is no movement of fluid at all
Diseases that Change Starling Forces
Nephrotic Syndrome: Increased permeability of glomerular capillaries to plasma proteins; results in increase πB (proteins are suppose to stay in circulation so they can draw water from interstitial spaces)
Urinary Tract Obstruction (Obstructive Uropathy):
Backs up tubular flow; results in increased PB
Golerular Filtration Rate
GFR will tell you how well your pt’s kidney are functioning ; Kf in glomerular filtration rate is usually 12ml/min/mmHg
GFR= Kf x ΔP
Kf= range from 10-15 ml/min/mmHg; about 12 usually (must be given to you on exam)
Kf= 12 ml/min/mmHg
Normal value of GFR: 90-140 ml/min; dependent on gender, size, and ethnicity
ΔP= (PGC+ πBS) – (PBS+πGC); if any of these pressure are changed this will affect your ΔP; eventually affects your GFR
Glomerural Pressure Variation
Constrict afferent:
Decrease Renal plasma flow (RPF)
Decrease GFR
Dilate Afferent:
Increase RPF
Increase GFR
Constrict efferent:
Decrease RPF
Increase GFR
Dilate efferent:
Increase RPF
Decrease GFR
Filtration
Movement of solutes from glomerular capillaries to Bowman’s space
Reabsorption
Returns most fileted solutes to circulation (want to keep these things)
Secretion
transports from peritubular capillaries and vasa recta into the tubular lumen (want to get rid of these things) (Secreted into lumen and then excreted)
Excretion
Solute in urine due to filtration, secretion, reabsorption (sum of 3 processes)
Overall solute movement
- Filtration- From the glomerular capillary and into the bowman’s space
- Ultrafiltrate is going to flow into the proximal tubule (reabsorption of solutes that we want to keep) (secrete things we don’t want to keep)
- Loop of Henle- (reabsorption in the descending limb (impermeable to solutes), mostly water); Thin and thick ascending (reabsorption of solutes only b/c they are impermeable to water)
- Distal tubule- reabsorption or secretion of solutes and water (early tubule: absorption of solutes only b/c impermeable to water) (distal tubule is permeable to solutes and water if you are in dehydrated state)
- Collecting Duct (reabsorption or secretion) as well as excretion (only part of body to do this)
- Note: Potassium is the solute that is present throughout this entire process; nephrons are making sure your body is in balance; secretes and excretes to regulate levels
If GFR is too high….
If GFR is too low…
If GFR is too high: Needed substrates cannot be reabsorbed quickly enough and are lost in the urine
If GFR is too low: Everything is reabsorbed, including wastes that are normally disposed
What does afferent arteriole constriction do to GFR?
Afferent arteriole construction: Glomerular hydrostatic pressure decreases, decreasing filtration–> decrease GFR
What does efferent arteriole construction do to GFR?
Efferent arteriole constriction: Glomerular hydrostatic pressure increases, increasing filtration–> increase GFR
Auto-Regulation of Renal Blood Flow
Auto regulation: GFR and RBF constant 80-180mmHg
<80mmHg- reduced renal blood flow
>180mmHg- severe hypertension; auto regulation stops
Myogenic feedback mechanisms
Increase BP, increase blood flow, increase GFR–> Increase Afferent Arteriole Stretch
–> Calcium channels open(effects the smooth muscle of the cells) –> Increase Afferent Arteriole Contraction
Tubulgolmerular feedback mechanisms
Involves macula dena and vasoactive substances (adenosine, kinins, PG’s) to constrict afferent/efferent arterioles
Macula densa are sensors; sense tubular flow through concentration of sodium chloride; sense increase in flow; send info to Juxtamedullar cells and signals the release of adenosine; vasoconstrictor in kidneys, but a vasodilator everywhere else
Reduction in NA sends signals to juxta cells and say GFR is too low; renin is released; catalyzer that turns angiotensionogen to Angiotensin 1; ace then convers Angiotensin 1 to Angiotensin II; Angiotensin II constricts the efferent arteriole (build up causes backup of blood, which increases the filtration rate, which increases GFR)
Concentrating and Diluting Urine
Water balance (controlled by concentrating and diluting the urine)
Water gain (2.2L/day through food and drink)= Water loss (skin, lungs (insensible water loss) urine, and feces)
Descending limb: only permeable to water (less dilute) and water goes into interstituim and vasa recta; Tubular fluid is becoming more concentrated
- Tubular fluid is very concentrated by bottom of lip
Ascending limb: Impermeable to water so water does not leave; tubular fluid is becoming more dilute permeable to Na, Cl, K and get absorbed vasa recta (more dilute)
-Tubule fluid is dilute
If pt is dehydrated and needs more water absorption ADH is released; causes the opening of H2O channels on the distal tubule
- If pt is hydrated then ADH is NOT RELEASED and the urine is more dilute as it leaves the collecting duct
- 50-1200 mOsM urine excreted
Renin- Angiotensin-Aldosterone
Stimulus: JGA responds to love blood volume or BP (maybe due to dehydration or less of blood
Step 1: Release of renin catalyzes the creation of Angiotensin I, which is then turned into Angiotensin II by ACE in the lungs
Step 2: Angiotensin II is very potent arterial vasoconstrictor; constricts the efferent arteriole to back up the blood and increase the GFR
Step 3: AngiotensinII is stimulated by decreased arterial pressure, low Na+ intake (in addition it also helps increase Na reabsorption in proximal tubule, increase thirst, and stimulates aldosterone from adrenal cortex)
Step 4: Aldosterone: Increases Na+ reabsorption and K secretion by principal cell in the late distal tubule and collecting duct
ADH (Vasopressin) Secretion
- Involved in the regulation of body water content
- Secreted by posterior pituitary
- Allows for formation of water channels in the late distal and collecting duct increasing water reabsorption of water
Secretion stimulated by:
If plasma osmolarity rises 1mOsm/L (normal = 280-295 mOsm/L)
or
Hypovolemia >8% (blood volume)
Actions: reabsorbs H2O- increase urine osmolarity and decreases urine flow volume
Atrial Natriuretic Peptide (ANP)
Stimulation: High blood pressure stretches the heart chamber chamber of the heart and in response ANP is secreted by the RT atrium
- Inhibits reabsorption of Na+ and water- stimulates Na+ and water excretion–>blood volume is lowered and decreases BP
Normal whole-body daily sodium balance
Sodium has to be at normal levels for body to act properly ( Normal Na+ levels in extracellular fluid (ECF) is 140 mEq/L and 14 mEq/L in intracellular fluid (ICF)
Na+ is the major component of ECF compartment (plasma and interstitial fluid)- determine ECF volume–> plasma volume–>blood volume–> blood pressure
- Kidney’s maintain normal body Na+ content so NA+ balance: daily NA intake= daily Na+ ecretion
- ve Na+ balance: Na+ excretion <na> ECF volume expansion--> increase blood volume and blood pressure)</na>
-ve Na+ balance: Na+ excretion> Na+ intake (Na+ lost from ECF–>ECF volume contraction
–> decrease blood volume and blood pressure)
Nephron segments contribution to the reabsorption of filtered salt and water: Early Proximal Tubule
Early proximal tubule: Most essential solutes are reabsorbed with Na+: Glucose, amino acids, and HCO3-
Cotransport Mechanisms: Na+ reabsorption is coupled with uncharged molecules (glucose, amino acids, amino acids, phosphates, lactate, citrate)- accounts for 10% of Na+ reabsorption; H2O follows
Countertransport/Exchanger_:_ Na+/H+ antiport allows H+ secretion HCO3- (bicarbonate) reabsorption; HCO3- (bicarbonate) is the anion reabsorbed with NA+; accounts for 20-25% Na+ reabsorption
EARLY PROXIMAL TUBULE= NaHCO3 Reabsorption
Nephron segments contribution to the reabsorption of filtered salt and water: Late proximal tubule
Late proximal tubule:
Cellular component: Na+/H+ antiporter coupled to Cl- reabsorption and formate secretion; accounts for about 35% Na+ reabsorption
Paracellular component: Passive reabsorption of Na+ and Cl –
LATE PROXIMAL TUBULE= NaCl reabsorption
Nephron segments contribution to the reabsorption of filtered salt and water: Thick Ascending Limb
Thick Ascending Limb:
Cellular Mechanism: NA+/K+/2Cl- cotransporter on apical cell of epithelium; energy is derived from Na+ gradient with reabsorption of Na+ K+ 2CL-
Na+/H+ antiporter to allow for HCO3- (bicarbonate) reabsorption
Accounts for 25% of Na+ reabsorption
Nephron segments contribution to the reabsorption of filtered salt and water: Early Distal Tubule
Early Distal Tubule
Cellular Mechanism: Na+ CL- cotransporter; energy is derived from Na+ gradient with reabsorption of Na+ and Cl-
Accounts for 5% of Na+ reabsorption
Nephron segments contribution to the reabsorption of filtered salt and water: Late Distal Tubule and Collecting Duct
Late Distal Tubule and Collecting Duct
Principal cell: involved in NA+ reabsorption and K+ secretion
Alpha- intercalated: involved in K+ reabsorption and H+ secretion
Mechanism: Na+ channels; Na+ diffuses through the channels from its electrochemical gradient
- Account for 3% of Na+ reabsorption ; last two segments that sodium passes through before excretion; fine tuning area to nephron
- Adjustments to Na+ excretion are hormonally regulated by aldosterone- synthesizes Na+ channels to increase Na+ reabsorption
PCT= Bulk
LD/CD= Fine tuning
Tubuloglomerular Feedback
Macula densa cells part of juxtaglomerulus apparatus that sense tubular flow and GFR and send feedback signals to afferent or efferent arteriole to constrict/dilate to keep GFR at normal levels
Pathways:
Bp increase–> increase blood in kidney–> increase GFR–> flow into tubule is faster–> macula densa senses NaCl is high–> signals release of adenosine which constricts the afferent arteriole
Low kidney flow–> reduced tubular flow–>macula densa sense NaCl is too low–>signal the release of renin angiotensin (converted to Angiotensin I and then Angiotensin II) to help constrict efferent arterial resistance–> angiotensin II will stimulate aldosterone which will absorb more sodium and get the BP back up
What are the effects of decreased Na+ intake?
Sympathetic Stimulation: Activated in response to decreased arterial pressure
Nerves decreases Na+ excretion in 3 ways:
1) Decrease GFR and RBF; decreased filtered Na+ load for secretion
2) Direct stimulatory effect on Na+ reabsorption by renal tubules
3) Causes renin release–> increases Angiotensin II and aldosterone levels for reabsorption (Angiotensin II work in proximal tubule for Na+ reabsorption and Aldosterone works in the late distal tubule for Na+ reabsorption)
What are the effects of increase Na+ intake?
CHECK PHYSIOLOGY NOTES!
Atrial Natriuretic Peptide (ANP)
Atrial Natriuretic Peptide (ANP): increase in blood volume the RT atrium cause increase secretion of ANP which increases Na+ excretion and water loss in the form of urine
Increases GFR (dilate afferent/constrict efferent arterioles)
pH
Ph= -log[H+]
Acidemia
Low arterial ph (<7.35)
Acidosis
Process leading to a reduced pH
Alkalemia
High arterial pH (>7.45)
Alkalosis
Process leading to an increase pH
Volatile acid
Expired by the lungs
13,000-20,000 mM CO2/day metabolized from carbohydrates and fats
Non-Volatile (fixed) acid
RENALLY EXCRETED
40-60mM/day lactate, B-hydroxybutyric acid, acetoacetate, phosphoric,and sulphuric acid- form H+
Three primary systems used to regulate H+
1)Buffering systems of body fluids (instantaneous): Immediately combines with acid/base to prevent large changes in [H+]
2) Respiratory Response (within minutes to eliminate CO2): Within minutes to eliminate CO2 (H2CO3-) from body
3) Renal Response(slowest, but most powerful- to eliminate excess acid/base): Slowest- hours/days to eliminate excess acid/base (MOST POWERFUL REGULATORY SYSTEM)
Chemical buffers regulate pH
Buffer: any substance that can reversibly bind H+
HAßà H+ + A- (mixture of weak acid and its conjugate base OR a weak base and its conjugate acid) i.e. H2CO3 ⇔H+ and HCO3-
- First line of defense against any pH changes
- Buffered solution minimizes a change in pH, but does not prevent it
- Several buffering systems (ECF and ICF) and the sum= 7.4
Henderson-Hasselbalch Equation
To calculate the pH of a buffered solution
pH= [HCO3-] / PCO2
Buffers found in extracellular and intracellular fluid
Blood proteins, Inorganic phosphates (H2PO4/HPO4-)
Intracellular Buffers: Hemoglobin, ATP,ADP,Glucose-phosphates
HCO3-/CO2- Buffer System
Most important ECF Buffer:
- Bicarb concentrations are greater than the phosphates(HPO42-) and can be adjusted by the kidney
- CO2 acid form of buffer is volatile and can be expired by lungs
- pK is 6.1 close to ECF pH
Respiratory Compensation
Acts rapidly to prevent large changes in [H+] until kidney response; does not return [H+] all the way to normal; effectively gains 1-3pH units within 3-12 minutes; 1-2x greater buffering power than ECF buffers combined
With abnormalities: Compensates for changes in [HCO3-]
PαCO2= 40mmHg with normal [HCO3-]; pH=7.4; If decrease [HCO3-] will compensate by decreasing PαCO2 (hyperventilating) which returns pH to normal
Renal Compensation
Kidney compensates for changes in PαCO2 by adjusting [HCO3-] reabsorption; non-respiratory compensation done by H+ secretion or titrateable acid/ammonia excretion
3 Mechanisms to regulate ECF H+ Concentration
- Secretion of H+
- Reabsorption of filtered HCO3-
- Production of new HCO3- (via ammonia/titratable acid excretion)
REFER TO NOTES FOR ACCOMPANYING DIAGRAMS
Ammonia Buffering: Proximal Tubule
Proximal Tubule:
Glutamine metabolism will give 2 NH4 and 1 alpha KG
NH4+ Secretion on Na+ antiporter or as combined NH3 + H+ in lumen
2 new HCO3- absorbed
Ammonia Buffering: Thick Ascending
- NH4+ reabsorbed by cotransport for K+
- NH3 secreted into CD and binds H+ for NH4+ secretion
Ammonia Buffering: Collecting Duct
- Secretion of H+ via antiport will form 1 new HCO3-
- NH3 is lipidophilic and can move between cells
- H_ secreted will join wih NH3 and form NH4+ which is NOT lipid soluble and is trapped in lumen (Diffusion trapping)
- H+ is excreted as NH4+ with the addition of NEW HCO3-
Production of new HCO3- via titrable acid
Titratable buffering systems (i.e. phosphate) (40 mEq/day)
Titratible acid: H+ excreted with urinary buffers (phosphate)
Minimum urine pH is 4.4-4.5; if uring ph<4.4 H+ secretion stops/NH4+ excretion increases
Phosphate is the most important buffering system in this category b/c concentrated in tubules
AMOUNT EXCRETED AS TITRATABLE ACID DEPENDS ON THE AMOUNT OF AVAILABLE PHOSPHATE
85% of HPO42- filtered is reabsorbed leaving 15% to be excreted as titrateable acid in H2PO4 form
Metabolic and Respiratory Acid Base Disturbances
Metabolic Disturbances: Primary disorder with [HCO3-]
- Metabolic Acidosis: Increased [H-] and decreased [HCO3-]- more buffering
- Metabolic alkalosis: decreased [H+] and increased [HCO3-]- loss of H+/ gain of HCO3-
Respiratory Disturbances: Primary Disorder of CO2
- Respiratory Acidosis: Hypoventilation increases PCO2
Respiratory Alkalosis: Hyperventilation decreases PCO2
What are the two types of compensation?
Respiratory Compensation
Renal Compensation
If the acid-base disturbance is metabolic [HCO3-] what is the primary compensation response?
Primary response is respiratory to alter Pco2 (some renal days later)
If the acid-base disturbance is respiratory (Pco2) then what is the compensation response?
The compensation response is ONLY metabolic (renal) to alter [HCO3-]
Compensatory response is always in the what direction of the origional disturbance?
Compensatory response in always the same direction as the orgional disturbance
What are some causes of metabolic acidosis?
Primary disturbance: Decreased [HCO3-]
- excessive production of ingestion of fixed H-
- Less of HCO3-
- Inability to excrete fixed H+
What are some causes of metabolic alkalosis?
Primary: Increased [HCO3-]
- Loss of H+
- Gain of HCO3-
- Vomlume contraction alkalosis
What are some causes of respiratory acidosis?
Primary Disturbance: Increased CO2 retention due to hypoventilation
- Inhibition of the medullary respiratory center
- Disorders of respiratory muscles
- Airway Obstruction
- Disorders of gas exchange
What are the causes of respiratory alkalosis?
Primary Disturbance: Decreased CO2 due to hyperventilation
- Stimulation of the medullary respiratory center
- Hypoxemia
- Mechanical Ventilation
