MSAP Renal Physiology Notes

Question 1

Basic Functions of the kidneys

Answer 1

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

Question 2

Nephron

Answer 2

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

Question 3

Juxtamedullary Nephron

Answer 3

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)

Question 4

Cortical Nephron

Answer 4

more common

Bowman’s capsule is higher up in the cortex

No thin ascending limp

Unable to fully dilute/ filter urine

Question 5

Nephron associated vasculature

Answer 5

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)

Question 6

Filtration (factors that affect filtration)

Answer 6

2 components determine flux across glomerulus: 1) permeability and 2) glomerular filtration pressure

1. 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
2. Charge (15-35A: Cations>neutral>anions) (Remember pedicels are negatively charged!)

Question 7

Freely filtered molecules

Answer 7

passes readily through barrier into bowman’s space; [plasma]= [Bowman’s space]

Question 8

Non-freely filtered molecules

Answer 8

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

Question 9

Filtration barriers that impede movement of water and various solutes

Answer 9

• 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

Question 10

Filtration barriers that impede movement of water and various solutes

Question 11

Starling’s Forces

Answer 11

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)

Question 12

Hydrostatic Pressures

Answer 12

1. Hydrostatic pressure of Capillary (P_Gc): favors filtration; force that preventss water from entering the capillary
2. Hydrostatic pressure of intersttium (P_BS): opposes filtration/favors reabsorption (H₂O follows solutes- increase pressure- forces H₂O into capillary)

Question 13

Oncotic Pressures

Answer 13

1. _Oncotic pressure of blood (plasma) (_π_GC )- opposes filtration/favors reabsorption; major driving force in reabsorption (high concentration of proteins from differnet arterioles)
2. Oncotic pressure of interstitial fluid/Bowman’s space (__π_BS): favors filtration (+)- no proteins in bowman’s space (0 mmHg)

Question 14

Net force pressure

Answer 14

ΔP= (factors that favor filtration)- (factors that favor reabsorption)

ΔP= (P_GC+ π_BS) – (P_BS+π_GC) (have to use this version if oncotic pressure of bowman’s space is provided)

π_BS= Oncotic pressure of bowman’s space= usually zero or negligible

ΔP= P_GC- P_BS- π_GC (able to use this version of the equation if the oncotic pressure is negligible

P_GC= 45 mmHg (somewhat constant; usually around 45-60mmHg)

P_BS= 10 mmgHg (pretty constant as well usually about 10mmHg)

Question 15

Clinical Situation__: If a kidney stone blocked a renal calyx, how would this affect filtration pressure in the nephrons emptying into it?

Answer 15

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

Question 16

Diseases that Change Starling Forces

Answer 16

Nephrotic Syndrome: Increased permeability of glomerular capillaries to plasma proteins; results in increase π_B (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 P_B

Question 17

Golerular Filtration Rate

Answer 17

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= (P_GC+ π_BS) – (P_BS+π_GC); if any of these pressure are changed this will affect your ΔP; eventually affects your GFR

Question 18

Glomerural Pressure Variation

Answer 18

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

Question 19

Filtration

Answer 19

Movement of solutes from glomerular capillaries to Bowman’s space

Question 20

Reabsorption

Answer 20

Returns most fileted solutes to circulation (want to keep these things)

Question 21

Secretion

Answer 21

transports from peritubular capillaries and vasa recta into the tubular lumen (want to get rid of these things) (Secreted into lumen and then excreted)

Question 22

Excretion

Answer 22

Solute in urine due to filtration, secretion, reabsorption (sum of 3 processes)

Question 23

Overall solute movement

Answer 23

1. Filtration- From the glomerular capillary and into the bowman’s space
2. 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)
3. 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)
4. 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)
5. Collecting Duct (reabsorption or secretion) as well as excretion (only part of body to do this)
6. 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

Question 24

If GFR is too high….

If GFR is too low…

Answer 24

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

Question 25

What does afferent arteriole constriction do to GFR?

Answer 25

_Afferent arteriole construction_: Glomerular hydrostatic pressure decreases, decreasing filtration--\> decrease GFR

Question 26

What does efferent arteriole construction do to GFR?

Answer 26

_Efferent arteriole constriction_: Glomerular hydrostatic pressure increases, increasing filtration--\> increase GFR

Question 27

Auto-Regulation of Renal Blood Flow

Answer 27

_Auto regulation:_ GFR and RBF constant 80-180mmHg \<80mmHg- reduced renal blood flow \>180mmHg- severe hypertension; auto regulation stops

Question 28

Myogenic feedback mechanisms

Answer 28

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

Question 29

Tubulgolmerular feedback mechanisms

Answer 29

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)

Question 30

Concentrating and Diluting Urine

Answer 30

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

Question 31

Renin- Angiotensin-Aldosterone

Answer 31

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

Question 32

ADH (Vasopressin) Secretion

Answer 32

- 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

Question 33

Atrial Natriuretic Peptide (ANP)

Answer 33

_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

Question 34

Normal whole-body daily sodium balance

Answer 34

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 ECF volume expansion--> increase blood volume and blood pressure) -ve Na+ balance: Na+ excretion\> Na+ intake (Na+ lost from ECF--\>ECF volume contraction --\> decrease blood volume and blood pressure)

Question 35

Nephron segments contribution to the reabsorption of filtered salt and water: Early Proximal Tubule

Answer 35

_Early proximal tubule_: Most essential solutes are reabsorbed with Na+: Glucose, amino acids, and HCO3- ## Footnote **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

Question 36

Nephron segments contribution to the reabsorption of filtered salt and water: Late proximal tubule

Answer 36

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

Question 37

Nephron segments contribution to the reabsorption of filtered salt and water: Thick Ascending Limb

Answer 37

_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

Question 38

Nephron segments contribution to the reabsorption of filtered salt and water: Early Distal Tubule

Answer 38

_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

Question 39

Nephron segments contribution to the reabsorption of filtered salt and water: Late Distal Tubule and Collecting Duct

Answer 39

_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

Question 40

Tubuloglomerular Feedback

Answer 40

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

Question 41

What are the effects of decreased Na+ intake?

Answer 41

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)

Question 42

What are the effects of increase Na⁺ intake?

Answer 42

CHECK PHYSIOLOGY NOTES!

Question 43

Atrial Natriuretic Peptide (ANP)

Answer 43

_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)

Question 44

pH

Answer 44

Ph= -log[H+]

Question 45

Acidemia

Answer 45

Low arterial ph (\<7.35)

Question 46

Acidosis

Answer 46

Process leading to a reduced pH

Question 47

Alkalemia

Answer 47

High arterial pH (\>7.45)

Question 48

Alkalosis

Answer 48

Process leading to an increase pH

Question 49

Volatile acid

Answer 49

Expired by the lungs 13,000-20,000 mM CO2/day metabolized from carbohydrates and fats

Question 50

Non-Volatile (fixed) acid

Answer 50

RENALLY EXCRETED 40-60mM/day lactate, B-hydroxybutyric acid, acetoacetate, phosphoric,and sulphuric acid- form H+

Question 51

Three primary systems used to regulate H+

Answer 51

_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)

Question 52

Chemical buffers regulate pH

Answer 52

_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

Question 53

Henderson-Hasselbalch Equation

Answer 53

To calculate the pH of a buffered solution pH= [HCO₃-] / PCO₂

Question 54

Buffers found in extracellular and intracellular fluid

Answer 54

Blood proteins, Inorganic phosphates (H₂PO4/HPO₄^-) Intracellular Buffers: Hemoglobin, ATP,ADP,Glucose-phosphates

Question 55

HCO₃-/CO₂^- Buffer System

Answer 55

Most important ECF Buffer: - Bicarb concentrations are greater than the phosphates(HPO₄^2-) 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

Question 56

Respiratory Compensation

Answer 56

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-] P_αCO2= 40mmHg with normal [HCO₃^-]; pH=7.4; If decrease [HCO3-] will compensate by decreasing P_αCO2 (hyperventilating) which returns pH to normal

Question 57

Renal Compensation

Answer 57

Kidney compensates for changes in P_αCO2 by adjusting [HCO₃^-] reabsorption; non-respiratory compensation done by H⁺ secretion or titrateable acid/ammonia excretion

Question 58

3 Mechanisms to regulate ECF H^₊ Concentration

Answer 58

1. Secretion of H+ 2. Reabsorption of filtered HCO3- 3. Production of new HCO3- (via ammonia/titratable acid excretion) REFER TO NOTES FOR ACCOMPANYING DIAGRAMS

Question 59

Ammonia Buffering: Proximal Tubule

Answer 59

_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

Question 60

Ammonia Buffering: Thick Ascending

Answer 60

- NH4+ reabsorbed by cotransport for K+ - NH3 secreted into CD and binds H+ for NH4+ secretion

Question 61

Ammonia Buffering: Collecting Duct

Answer 61

* 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-

Question 62

Production of new HCO^3- via titrable acid

Answer 62

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

Question 63

Metabolic and Respiratory Acid Base Disturbances

Answer 63

Metabolic Disturbances: Primary disorder with [HCO3-] 1. Metabolic Acidosis: Increased [H-] and decreased [HCO3-]- more buffering 2. Metabolic alkalosis: decreased [H+] and increased [HCO3-]- loss of H+/ gain of HCO₃^- Respiratory Disturbances: Primary Disorder of CO₂ 1. Respiratory Acidosis: Hypoventilation increases PCO₂ Respiratory Alkalosis: Hyperventilation decreases PCO₂

Question 64

What are the two types of compensation?

Answer 64

Respiratory Compensation Renal Compensation

Question 65

If the acid-base disturbance is metabolic [HCO₃^-] what is the primary compensation response?

Answer 65

Primary response is respiratory to alter Pco₂ (some renal days later)

Question 66

If the acid-base disturbance is respiratory (Pco₂) then what is the compensation response?

Answer 66

The compensation response is ONLY metabolic (renal) to alter [HCO₃^-]

Question 67

Compensatory response is always in the what direction of the origional disturbance?

Answer 67

Compensatory response in always the same direction as the orgional disturbance

Question 68

What are some causes of metabolic acidosis?

Answer 68

Primary disturbance: Decreased [HCO₃^-] 1. excessive production of ingestion of fixed H^- 2. Less of HCO₃^- 3. Inability to excrete fixed H⁺

Question 69

What are some causes of metabolic alkalosis?

Answer 69

Primary: Increased [HCO₃^-] 1. Loss of H⁺ 2. Gain of HCO₃^- 3. Vomlume contraction alkalosis

Question 70

What are some causes of respiratory acidosis?

Answer 70

Primary Disturbance: Increased CO₂ retention due to hypoventilation 1. Inhibition of the medullary respiratory center 2. Disorders of respiratory muscles 3. Airway Obstruction 4. Disorders of gas exchange

Question 71

What are the causes of respiratory alkalosis?

Answer 71

Primary Disturbance: Decreased CO₂ due to hyperventilation 1. Stimulation of the medullary respiratory center 2. Hypoxemia 3. Mechanical Ventilation