Renal Physiology Flashcards by Karen Bianca Espinola

What is the net gain of water per day?

Zero: Fluid gained per day = fluid lost per day

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What do you call the maintenance of the internal environment compatible with life?

Homeostasis

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Which organ system contributes to homeostasis by adjusting water and electrolyte levels?

Renal System: mainly by producing urine

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What is urine?

Urine is an ultrafiltrate of blood

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Waste product from Proteins

Urea

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Waste product from Purines

Uric Acid

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Waste product from Muscles

Creatinine

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Waste product from RBCs

Bilirubin

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Excretion of variable amounts of water and sodium; Involved in RAAS

Blood pressure regulation

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Excretion of excess acids and bases

Regulation of Acid- Base balance

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Increases RBC production in response to hypoxia

Production of Erythropoeitin (EPO)

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Produces glucose during the starvation state

Gluconeogenesis

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Location of Kidney

T12-L3

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Weight of Kidney

150g

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Highly-fenestrated, responsible for GFR

Glomerular Capillaries

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Supplies O2 & glucose to the tubular cells

Peritubular Capillaries

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Secretes Erythropoietin (EPO)

Interstitial Cells

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Hairpin loop-shaped peritubular capillaries of the juxtaglomerular nephrons that participate in countercurrent exchange

Vasa Recta

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Capacity of the Urinary Bladder

600ml

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Urge to urinate

150ml

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Reflex contraction of the Urinary Bladder

300ml

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Bladder muscle

Detrusor muscle

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Internal Urethral Sphincter

Involuntary

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External Urethral Sphincter

Voluntary

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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:

``` Nephrin NEPH-1 Podocin Alpha-actinin 4 CD2-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?

Endothelium Basement membrane Foot processes of Podocytes

What is the charge of this charge barrier and what does it block?

Negative | Prevents 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 DM HPN

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?

``` EDFR PGE2 PGI2 Bradykinin Glucocorticoids ANP BNP ```

Which hormone will preserve GFR?

Angiotensin II (preferentially constricts efferent arteriole)

Which hormone will increase Renal Blood Flow (RBF)?

Histamine Dopamine ANP BNP

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 gradient Membrane permeability Time

"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 Acids | 66% 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

PCT TAL LH DT

Site of Action of Catecholamines

PCT TAL LH DT/CD

Site of Action of Vasopressin

DT | CD

Site of Action of ANP/BNP

DT | CD

Site of Action of Uroguanylin, Guanylin

PCT | CD

Site of Action of Dopamine

PCT

Site of Action of PTH

PCT TAL LH

Effects of Aldosterone

Increase Na, water reabsorption | Increase 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 reabsorption Increase Ca reabsorption Stimulates 1 Alpha Hydroxylase

What are the triggers for ADH secretion?

Increased Plasma Osmolarity Decreased Blood Pressure Decreased 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 level | High Urine level

If a substance has a low clearance, what are the blood and urine level of this substance?

High Blood level | Low 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

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 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

Hyperkalemia | Hypercalcemia

Can cause weakness

Hypokalemia

First line of defense

Movement of K across ECF to ICF

Factors that shift K into cells

Insulin Aldosterone B-Adrenergic Stimulation Alkalosis

Factors that shift K out of cells

``` Insulin Deficiency Addison's Disease B-Adrenergic Blockade Acidosis Cell lysis Strenuous Exercise Increase 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 doet Hyperaldosteronism Alkalosis Thiazide diuretics Loop diuretics Luminal anions ```

Causes of decreased K secretion

Low K diet Hypoaldosteronism Acidosis K 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 Phosphate Decreased ECF, BP Metabolic Acidosis Vit D3

Factors that alter renal calcium excretion: Increased excretion

Increased ECF, BP Decreased PTH, Plasma Phosphate Metabolic Alkalosis

Trio of Electrolytes: High H levels

Hypercalcemia | Hyperkalemia

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 Wall Na-K-2Cl pump in the TAL LH Slow 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 quickly Vasa 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, Angiotensin Decrease Blood Volume, BP Dryness of mouth

Control of Thirst: Decreased thirst

Increased Blood Volume, BP Decreased Osmolarity, Angiotensin II Gastric 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 Systems Respiratory Center Kidneys

Mechanisms of Renal Regulation of Acid-Base Balance

Secretion of H Reabsorption of filtered HCO3 Production 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)