A & P 3: Exam 2

Adult Body water

45-60% water

Content varies between tissues

• Bone: Low = 22%

• Fat: Low = 10 %

• other Typical Tissues 70-80%

Obesity: low water content

S#x: females have higher content

Age: The older the dryer

Infant: High percentage 75%

Water compartmentalization % of Total Water

Intracellular Fluid: 65%

Extracellular fluid: 35%

Interstitial Fluid: 25%

Plasma & Lymph = 8%

Others (CSF, Synovial joint, Eye circulation) = 2%

Osmolarity

Total Solute Concentration = 300 mM

• Chug water: osmalarity goes down

• Salty food: Osmolarity goes up

ICF = ECF

Plasma Osmolarity > Interstitial fluid Osmolarity

Solute composition in ECF & ICF

ECF:

Sodium (Na) = 145 mM

Chloride = 103 mM

Potassium (k) = 4mM

ICF:

Sodium (Na) = lower

Chloride = lower

Potassium (k) = higher

Osmosis

Special case of simple diffusion

Includes:

• Isotonic = 300 mM (regular body) (no net exchange)

• Hypotonic < 300 mM (chugging watter)

• Hypertonic > 300 mM (salty food)

Water goes from high to low water

350 goes into 300

Water Budget in Body Inputs

Typical Daily Turnover ~ 2500 mL/day

Inputs:

• Drinking & Eating = 2300 mL/day (8 glasses og H2O per day = preformed water) can change ex: eating watermelon ↑

Metabolic Water Production

200 mL/day

• Equation of life: O2 + Fuel → CO2 + ATP + Heat + H2O

• Another form of water production per day made by body

• can make more by eating & drinking (needed)

Water Budget in Body Output

Sensible (sweating) Perspiration ~ 100mL/day

• sweating via sudoriferous glands

• eliminates heat by evaporation

• controlled by Thermoregulatory center (in hypothalamus)

Variable:

• increases with heat and activity

• blood is now diluted

Insensible Perspiration

Sweat from the lungs (Respiratory water loss) or skin (Transcutaneous water loss)

700 mLDay

• RWL is high in cold and dry activity

• when when breath cold air we need to warm it up with water

• Skin is gonna be highest when its hot and dry

• dryness evaporates water off from skin

Air is Desicatting (more dry than you)

Saltwater = lose water (dehydrated swimming in ocean)

Freshwater = gain water

Fecal water lost

Fecal matter is ~ 70% watr

• lose abt 200 ml/day (inevitable)

KIdney

lose about ~1500 mL/day

• decreases w/ dehydration (vice versa)

• possible to overhydrate (can lose goodies)

cannot make water but can preserve/conserve it to minimize lost of water

Fluid imbalances: Dehydrated

input of water < output of water

• leads to hypovolemia → hypotension (low pressure)

• pressure always follows volume

• loser more water than salt

Can lead to hypetonic plasma &

• Cardiovascular system increases Arterial Pressure (Acute/Short term)

• Kidney (long term): takes longer to filter

• Ultimately requires: behaviour (hormones change, makes us thirsty abd seek out water)

Hypertonic plasma

Happens when the body sweats so we lose more water than solutes

• (drink water w/ a little salt) to balance

Fluid imbalances: Overhydration

Input > Output

Leads to:

• Hypervolemia -» Hypotension

• dilutes the plasma (hypotonic plasma < 300 mM) & blood (swells up the cells) CAN DIE FROM THIS

Input isn’t regulated by the body: have to pee it away

• overworks kidneys

Drinking 1L of water: gut absorbs all of it

Compensation:

• Acute: Cardiovascular can minimize pressure increases

• Chronic: Kidney rapidly eliminate excess water

Renal System

Balances water: Renal Regulates & Balances Blood Volume & Pressure

• Balances Individual Ion Concentrations & Total Osmolarity (sodium, chloride, calcium, potassium, magnesium, hydrogen, bicorbonate)

• Eliminate Wastes from Blood

• Directly Regulates Plasma

• Indirectly Affects All ECF Composition and Volume

Produces hormones:

• EPO (Erythropoietin)

• activates Calcitriol (Vitamin-D Pathway & Calcium Homeostasis) ON EXAM

Structure of the kidney

Very small up to 1% of Body Mass

• blood flow is exceptionally high here (16-20% of Cardiac Output)

• high mass metabolic rate (not propotionate)

• one of the most active organs per gram

• doesnt use as much oxygen as brain

Inputs & Outputs:

• Renal Artery (Major input)/ Vein (output)

• Ureter→ drain vein to bladder

• Efferent/Motor Nerves:

• Lymphatic Drainage: fluid out

• Adipose Padding: Mechanical Protection

Nephron

The functional unit of the kidney & reabsrobs ~ 99%

• includes: corpuscle + tubule

Associated Vasculature: (in it’s order of flow)

- Afferent Arterioles

- Glomerular Capillaries

- Efferent Arterioles

- Peritubular Capillaries (surrounds tubule, has net reabsroption)

- Renal Venules

Kidneys general abt 100 mL per min and reabsorbs

includes Portal System: 2 capillary beds in series (#2 OF 3)

Corpuscle Function: Nephron

a capsule that has the glomerulus (a modified capillary) that produces filtrate

• goes down the tubule for processing

Two ways:

1) Reabsoption: reabsorb fluid from tubule then reabsorb in pertubular capillary & secretes some of it into interstitium into the tubular filtrate

• what isn’t reabsorb will go into the urine

2)

Reabsorption: Tubule Filtrate à Interstitium

à Peritubular Capillaries

- Secretion: Peritubular Capillaries à Interstitium

à Tubule Filtrate

- Excretion: Final Product = Urine

Filtration by Glomerulus equation

The plasma is filtered to the capsular space across the filtration membrane

• the rate filtration that is formed by both kidneys abt 100 ml/min

Rate of Filtation = Glomerular Filtration Rate

GFR (mL/min) Proportional to: Kf Net Filtration Pressure (NFP) * Renal Plasma Flow (RPF)

GFR (mL/min) Proportional to: Kf * [(Pglomerulus – Pcapsule) – (πGLOMERULUS – πCAPSULE)] * Renal Plasma Flow (RPF)

• Kf = Glomerular Filtration Coefficient = HIGH = (High Surface Area & High Hydraulic Conductivity) very leaky due to gaps

• Net Filtration Pressure (NFP) = Outward Hydrostatic > Inward Osmotic Pressures

• fluid from filtration is > than fluid from reabsorption

• typical capillary = 0.1% (60 mmHg)

• renal plasma flow @ rest = 20% (High Filtration Fraction = Kf * NFP)

• high glomerular pressure in comparison to typical capillaries

• High osmotic reaborption due to reduced Filtration of moderately sized proteins

• These forces offset each other: Typical Glomerular NFP = 10 mmHg

Result: High Filtration Fraction

Result: GFR is High (110 mL/min)

• GFR = Filtration Fraction = Renal plasma Flow

Measures of Renal Filtration at rest ON EXAM very important

Cardiac Output

• 5 L/min

Renal Blood Flow (RBF)

• 20% of cardiac output A rest = 1L/min

Renal Plasma Flow (RPF)

• 55% of RBF

• RBF = 0.55 L/min = 550 mL/min

Glomerular Flitration Rate GFR

• total filtrate formation in both kidneys

• 110 mL/min (lots of fluid)

• Total Plasma Volume filtered every 25 mins

Filtration Fraction

• GFR/RPF = 20% typical

• GFR = RPF x FF = RPF x (NFP x Kf)

• GFR = RPF x (Pglomerulus)

Rate of Filtration by Glomerulus

filtratiom membrane includes the capillaries

• the basement membrane includes the visceral capsule which have podocytes on them which allows selective filtering

• plasma comes out of blood but NOT plasma proteins

Selective filtration of the glomerulus

Selectively limits what is filtered and restricts movement accross filtration membrane so that we don’t have to reabsorb it!

• formeed elements: Medium/Large Plasma Proteins: (Albumin, Glbulins, Fibrinogen)

• Complement & Antibodies

• Medium/Large Anions

• Size and negative charge/Hydrophobic solutes bound to plasma protein (thyroid hormones)

• clotting factors stay in the blood

Non-selective filtration by glomerulus

Things that get filtered

Small things (positive & negative) always get filtered into the filtrate

• ex: glucose, free amino acids, ions (Na, K, Cl, Ca, H+, HCO3-, Phosphates, Sulfates)

only POSITIVE medium cations things are filtered

• Toxins, waste products (urea, urobilinogen, etc)

• free hormones like (ADH, oxy, ALD)

• Large things NEVER filtered

Changes in Glomerulus Filtration Rate

1) Arterial Pressure

• “autoregulation” minimizes changes in renal blood flow and glomerular pressure despite changes in arterial pressure

• showcases that → Glomerular pressure is CONSTANT! despite arterial pressure unless it is going down

Autoregulation of GFR

Has two ways

1) Myogenic mechanism = intrinsic property of smooth muscle

• resists large sudden changes in blood flow

• ex: walking with your hands → blood rushes to brain w/vasodilation = alkalosis (trys to maintain pressure however)

2) Turbuloflomerular Feedback from Juxtagolumerular Appartatus

• Adjusts GFR to medoerate and constant level under normal conditions

Exception: Arterial Hypotension

• GRF decreases dramatically

• reflects decrease in golmerular pressure causing dramatic decrease in urine production

• urine is proportional to arterial pressure

Severe hypertension?: no increase of GFR

• urine can still increase

• can lose viable solutes

Sympathetic stimulation of Renal Activity

Stimulation inhbits renal activity

• ex: exercise causes alpha-1 vasoconstriction of Afferent arterioles (decreases capillary pressure + NFP + filtration fraction) which is below 20% at resting

• decreases renal blood flow/renal plasma flow

• maintains arterial blood pressure to supply active heart and skeletal muscle

• decrease Pglomerulus → decreases GFR

Sympathetic stimulation w/ a Hemmorrhange

Maintains sufficient blood pressure to perfuse other organs

• depends on how hydrated you are

• lower GFR

• due to Alpha-1 vasoconstriction of afferent arteriole

• efferent arteriole dilation is due to lack of SNS not activation PSNS

• osmolarity changes a little, decrease in volume

Processing of flitrate in the tubules

The filtrate is a combination of Good and bad things,

• Keeps good solutes (reabsorb) and gets ride of bad solutes (not reabsorb)

• both will enter the urine

Primary Tubule Segments

Divided into 5 segments

• Proximal Tubule

• Loop of Henle which includes (thin Descending loop and thick Ascending loop)

• Distale Tubule

• Collecting duct (tubule): does process

• Papillary duct: No processing occurs here

Reabsorption of

Most filtered solutes are reabsorbed (99%)

• Goes from the filtrate in the tubule, reabasorbed in thto the peritubular capillaries → across the tubular epithelium, to the interstium (intersgtital fluid)

• this process requires a Transport Across Tubule Epithelium (2 types)

1) Transcellular

2) Paracellular

Transcellular reabsorption Transport

Crosses both luminal (apical) and Basolateral (basal) membrane causing reabsorption

• does this with carrier proteins and channels which is driven by sodium/potassium ATPase (on basal membrane

• drives sodium transport on apical membrane

• soidum potassium ATPase is found on the basal membrane and we co-trans with this a lot

• an example of transcytosis

Transcytosis

Slow and metabolically expensive

• are subject to saturation

Paracellular

sneaking between epithelial cells

• has loose jundctions of some tubules allows this type of passive diffusion

• often driven by gradients created by transcellular mechanisms

Good solutes

the solutes that are filtered from the blood and returned/filtered to the blood

• most are good, if not filtered no problem, stays in the blood

• - ex: formed elements + Plasma proteins (albumins)

If it is freely filtered it must be reabsorbed

• low amt of solutes are good

• Typical Hydration: 99% Reabsorption

Bad solutes

wastes, toxins and excesses are NOT reabsrobed = remains in tubular fluid (capillaries) and excreted into the urine

• excess solutes are bad

Dehydrated

water is reabsorbed more completely: Increases to 99.9% Reabsorption

- Urine Flow Rate Decreases = 0.01 ml/min

- Results in Concentrated Urine Solutes (lots od wastes) = Increased Specific Gravity

- Maximum [Urine] = 1200 mOsm

• increases in osmolarity

• more water is lost than solutes

• decrease in volume

Overhydrated

Water is now bad means decrease in reabsorption

- Ex. 90% Reabsorption

- UFR = GFR x 10% = up to 10 mL/min

- Diuresis:

• decrease in osmolarity, increase in volume

Normonatremia

where 99% Filtered Sodium is reabsorbed

• 1% lost of avg

• normal volume and osmolarity

Hypernatremia

is an excess Sodium Consumption causing Sodium to be “Bad”

• Decrease % Reabsorbed to = 98% Reabsorbed (usually 99% so this # is stil high)

• usually we pee it away and dont retain it

• results in Natriuresis: increases sodium excretion causing a secondary diuresis (bc water follows salt)

• increase in volume, increase in osmolarity in blood

Hyponatremia

When sodium levels are low

• majority of sodium is now vastly reabasrobed → increases back to 99.9% reabsorption

Free water soluble Hormones

also eliminated by the kidney on the regular

Are freely filtered (has a short half life b/c not reasborbed)

• Larger Protein Hormones Filtered at Lower Rates = Moderate half Life.

• why? we dont want the hormonal effect forever

• if we need more hormones we can make it

• small hormones are filtered easier

• hydrophilic (water loving) = secreted easier

Hydrophobic Hormones Bound to Plasma Proteins

Only free Fraction can be Filtered and Excreted.

• Lost in Urine at Relatively Lower Rate = Longest ½ Life.

• ex: thyroid hormone

• bigger/hydrophobic hormones are harder to secrete

Osmosis

The reabsorption of most water

• across tubular epithelium into → interstitium → across peritubular capillaries

• water follows reabsorbed solutes (follows salts/solutes) = lower to higher osmolarity

• tubular fluid equilibrates with interstitium

• some tubule segments ar enot water permeable and this wont take place there

Secretion

frome the peritubular capillaries pumped into the filtrate

• how we get rid of stuff, putting it into the filtrate and out into the urine

• peritubular capilaries → interstium → across epithelium → filtrate

• via carrier mediated transport (very specific stuff only)

• can include “bad stuff”: wastes, toxins, & excesses/too much acid (we dont want things to accumulate)

• must be secreted if not filtered by glomerulus

• or secreted in addition to being filtered = filtered + secreted

Excretion of urine

what is lost in the urine

• filtered - reabsorbed + secreted

• always includes some water (we cant pee chunks)

Urine Flow Rate (UFR)

UFR = GFR x 0.01 (1%) what is peed away

ex: UFR = 110mL/min (0.11L/min) x 0.01 = 1.1 mL/min (remember units b/c TESTED)

• higher GFR → generally higher UFR

• % of reabsoprtion varies depending on hydration

Solute excretion

Leads to inevivatble water extcretion

• called secondary diuresis

ex: natriuresis → diuresis

• water follows solutes

Peritubular Capillaries

Reabsorbs solutes and water from interstitum

• all good stuff from tubules

• lots of solutes and water

• everytime solutes are being reabsorb, water follows via osmosis

Mechanism for Peritubular Capillaries

Blood within efferent arteriole goes in

• drops in peritubular pressure (low) and increases osmotic gradient (high

• Normal blood = 20% filtrate

• High plasma proteins

• low pressure

• net filtration pressure (NFP) = negative

• oxygen levels: high, due to passive filtration

Why are fluid balance challenges “complex”?

becauase the body must regulate both osmolarity (solute concentration) and volume/pressure at the same time, using different systems

• body uses seperate receptors for volume and osmolarity b/c they measure diff problems and allow body to respond more precisely to each

• when receptor detect a change it sends signals that trigger appropriate physiological responses depending on situation

• complex bc it involved 4 diff hormones and different mechanism in different kidney tubule segments

• each hormone acts on diff parts of the nephron to adjust fluid and electrolyte balances

Baroreceptors

Helps detect changes in volume and pressure in the kidneys, arteries and the heart

What detects osmolarity

Osmoreceptors in the hypothalamus

• regulating volume and osmolarity is not enough, addition regulation is required

• ions like Na⁺, K⁺, Cl⁻, Ca²⁺ and pH (acid-base balances)

• ions affect nerve function, muscle contract and fluid balance

The renin Angiotensin system (RAAS)

System is triggered by low blood pressure in renal arterioles

• juxtaglomerular cells in kidneys release renun

• renin converts angiotensiongen (from liver) to Angiotensin I

• Angiotensin 1 converts into Angiotensin II

Angiotensin II effects

causes vasoconstriction leading to highblood pressure

• stimulates aldosterone increase sodium (Na+) + water absorption

• stimulates ADH increasing water reabsorption

• stimulates thirst

results: high blood volume AND high blood pressure

Angiotensin II target and role

Role: Active hormone that responds to low blood pressure and a primary stimulus for thirst (dehydration)

Targets:

• systemic arterioles

• systemic veins

• kidney (afferent & efferent arterioles, proximal tubule)

• Hypothalamus: Stimulates thirst and provokes behavioral acquisition of water and drinking

• Adrenal cortex: Stimulates Aldosterone Secretion (RAAS)

Overall effect:

• Increase in blood pressure + maintain kidney filtration

Angiostensin II and systemic blood vessels

causes vasoconstriction of arterioles which increase systemic resistance which causes an increase in blood pressure

• venoconstriction equals to increase venous returns and increase blood pressure

• Ang II squeezes BOTH pipes, but squeezes the OUT pipe (efferent) to SAVE filtration

Angiotensin II constricting afferent arteriole

Causes decrease in renal plasma flow, glomerular pressure, and GFR

• only affected by the SNS

Angiotensin II constricting efferent arteriole

causes a bigger decrease in renal plasma flow, BUT

• maintains glomerular pressure prevents GFR from dropping to zero

SUPER IMPORTANT

• this helps counteract afferent constriction helping…

• maintain glomerular pressure maintain GFR despite low blood floor

• without it → GFR could go to zero

Angiotensin II affect on Proximal Tubule

Direct effect: Increases the solute reabsorption esp sodium and other salts

• indirect effect: Increase in water reabsorption

• Net effect: Rentention of both causing reabsroption of plasma from the filtrate back into the body where its supposed to be (b/c we are already low on volume)

Aldosterone (ALD)

It is a hydrophobic Mineralocorticoid produced in Adrenal Cortex that is stimulated from Angiotensin 2 and high potassium levels (hyperkalemia) BC od dehydration

• hypokalemia: not a stimulus for aldosterone

Target: Principal Cells of Distal Tubule

Effects:

- Increase Sodium (Na+) Reabsortion

- Increase Potassium (K+) Secretion (peed away by hyperkalemia)

- Net Solute Reabsorption: Sodium Reabsorption > Potassium Secretion (3 to 2 ratio) 3 sodium out 2 potassium in

• also increase absorption in water

• Indirect Effect?: water reabsorption

Anti-Diuretic hormone (ADH)

Origin:
Posterior pituitary (extension of hypothalamus)

Stimulus (PRIMARY):
high Plasma osmolarity (detected by hypothalamic osmoreceptors) - Example: Dehydration

→ High osmolarity → ↑ ADH release

Targets: Kidney causing increase in water reabsorption (anti-diuretic hormone) low urine output and no direct solute reabsroption

Results: in low plasma osmolarity and high blood volume

• this hormone increases in response to Dehydration

Atrial Natriuretic Peptide/Hormone (ANH)

this hormone is stimulated by too much volume (Hypervolemia) causes body to pee away the sodium causing diuresis (peeing away fluid)

• comes from the atria of the heart

• chemical structure: peptide

Targets: Kidney and Juxtaglomerular apparatus inhibiting renin secretion (suppresses angiosin 2)

• inhibits net solute; inhibiting solute reabsorption (so we dont absorb more volume;water)

• indirect affect: diuresis

Atrial Natriuretic Peptide/Hormone (ANH) and blood vessels

causes systemic arterials to vasodilate and if pressure is too high it will decrease arterial pressure increasing capillary pressure

• this increases filtration making fluid move out of plasma into the interstitium

Affects the kidneys causing

• afferent arteriole vasodilation

• increases glomerular pressure, GFR, and filtration fraction ultimately increasing urine formation

• ultimately, ↑ urine output

• ↓ plasma volume

• ↓ blood pressure

Brain Natriuretic Peptide works similarly (released from ventricles)

During hypervolemia (high ANP), what happens to ADH, Ang II, and Aldosterone?

• Atrial Natriuretic Peptide: ↓

• Angiotensin II: ↓

• Aldosterone: ↓

👉 Because the body is trying to lose fluid, not retain it

Normovolemia (baseline)

Atrial Natriuretic Peptide ADH: normal (baseline)

• Angiotesin II: low baseline

• Aldosterone: low baseline

Proximal tubule

a very active tubule (due to mass reabsroption of glucose, Na+, Water, nany solutes) and is one of the longest segments that emerges from the glomerulus also reabsrops peptides

• secretes plasma - plasma protein

• this tube reabsorbs 65% of solutes

• pumps sodium outwards by using ATP

plays in Glucose Reabsorption

• 1. Basolateral (blood side):

  • Sodium-Potassium ATPase pumps Na⁺ out
    👉 Creates low Na⁺ inside cell

  2. Apical (tubule side):

  • Na⁺ + Glucose symporter (SGLT)
    👉 Glucose enters cell using Na⁺ gradient (secondary active transport)

  3. Basolateral exit:

  • GLUT transporter
    👉 Glucose leaves cell → blood (facilitated diffusion)

Driven by the Na⁺ gradient created by the Na⁺/K⁺ ATPase

transport maximum (Tm) of glucose

The maximum rate at which glucose transporters can reabsorb glucose

Normally:

• Plasma glucose ≈ 90 mg/dL

• Glucose is freely filtered

• 100% reabsorbed in proximal tubule
  👉 No glucose in urine

Glycosuria

When plasma glucose exceeds the transport maximum and it cant leep up

• the excess glucose stays in filtrate causing diuresis (exretion)

How is glucose reabsorbed

• Apical: Na⁺-glucose symport (secondary active transport)

• Basolateral: GLUT (facilitated diffusion)

Amino acid reabsorptiomn in proximal tubule

Freely filtered from blood

• Apical membrane: Na⁺ + amino acid symport

• Basolateral membrane: Facilitated diffusion into blood

• Occurs in proximal tubule

• Saturatable (has a Tm)

Similar to glucose reabsorption

Protein Reabsorption in the Proximal tubule

1. Apical surface:

• Peptidases break peptides → amino acids

2. Small peptides:

• Reabsorbed via transcytosis (endocytosis → exocytosis)

• Slow and easily saturated

• Normally minimal protein in filtrate

Easily saturated because transcytosis is…

• slow, energy expensive, not designed for large protein loads

Proteinuria

Due to kidney damage (ex: inflammation) causing increase in protein filtration

• reabsroption mechanism becomes overwhelmed/saturated

• protein “spills” into urine

Water Reabsorption in the proximal tubule

Promixmal tubule is highly water permeable has aquaforins

• moved by osmosis

• water follows solutes (esp Na+)

• Osmolarity remains at 300 m0sm, so it stays the same solutes are reabsorbed, water follows proportionally

Angiotensin II effects on the Proximal tubule

stimulates and increases Sodium (Na+)/Potassium (K+) ATPase

• due to a low volume content, more water will follow by osmosis when Angiotensin is high

• increases solutes reabsroption from 99% to 99.9%

Goal: maintain plasma volume = maintain arterial blood pressure minimizing loss of water

• majority if waste/toxin secretions occur here + hormones/vitamins and drugs

• Many not filtered easily so cannot be excreted by filtration alone

Hypovolemia

Leads to hypertension increasing angiotension II formation

• stimulates Na/K ATPase

• Increases % sodium reabsorption → more water follows osmotically

• Maintains plasma volume = blood pressure

Afferent and efferent arteriolar vasoconstriction

Decreases renal plasma flow and decreased GFR

Hypervolemia

Causes hypertension, drinking too much water can lead to decreased renin secretion compared to regular tonic levels

• decreases angiotensin II

• Which decreases Na+/water reabsorption: only 98%

• Which doubles natriuresis and diuresis

Chronic Hypertension and hypervolemia

Theres a pathology so we treat it with ACE blockers which inhibits ACE enzymes

• decreases angiotensin II formation

• Increases natriuresis and diuresis

• Decrease in plasma volume

Loop of Henle

Thin loop that descends into medulla

• composed of descending (thin) and ascending (thick) loop

• Concentration gradient increases within deeper medullary interstitium: primarily NaCl and Urea

• Up to 1200 m0sm

Descending loop

A thin loop from the loop of henle that is made of simple squamous epithelium

• no active transport here

• Has a very high water permeability (water is reabsorbed here) but little solute permeability

• Surrounding osmolarity increases from 300 to 1200 m0ms/L

• Osmosis: filtrate equilibrates with medulla

• Bottom of juxtamedullarly loop → filtrate =

Thick Ascending loop

It is not permeable to water (does not have aquaforins)

• does not exchange its water with the interstitium

• has a double (not single) membrane

• Has a lot of solute reabsorption taking place

• It is hypertonic: abt 150 m0ms

• An active segment

Has a specific transporter:

• reabsorbs Na+ out of lumen/for every 2 Cl- (becomes positive luminal charge)

• Calcium (Ca+), magnesium (Mg+), Potassium (K+) are reabsorbed too (ON TEST)

• This is called Paracellular reabsorption

Effect?

• causes further dilution and solute reabsorption only

• Decreases osmolarity to 150 mOms

• Concentration of filtrate goes down at top of the loop

• Causes hypotonic filtrate

Juxtamedullary loop

Maintains medullary gradient

• primarily concentrations of urea and Na+/Cl-

• are collecting ducts that transit the medulla allowing for potential reabsorption here

Cortical loops

Shallow loops

• are collecting ducts that transit the medulla allowing for potential reabsorption here

Early distal tubule

This is the early portion of the Distal tubule

• less activity and metabolism compared to the proximal tubule

• A unique NaCl transporter for reabsorption

• Uses sodium potassium ATPase to drive out sodium

• Sodium is accompanied by chloride ion to go in?

• 1 to 1 ratio of Na and Cl does not create a luminal charge

• Target of common diuretic that blocks NaCl ???

• Water impereable so abt 100 m0ms

later Distal Tubule

Contains important cells: Principle cells

• potassium here is not able to love across membrane making it increase in concetration of the cell

• Sodium still moves out and is reabsorbed using ENaC (an apical epithelial sodium channel)

• driven by by Basal Na/K ATPase

• Ratio of 3 Na/2K+

• Net solute reabsorption or secretion????

• Further dikutes to 50 mOms bc its water impereable

High aldosterone levels?

Due to increase in angiotensin II and hyperkalenia which decreases in volume pressure and increase in potassium (Na/K ATPase activity) and ENac expression

• effect increase Na+ reabsorption and K+ secretion

• Effect: we reabsorb more water but still water impermeable

• causes hypervolemia

• Side effect questions on test

Hyperaldosternoism

Causes edma/swell causing hypoalkemia (due to excess potassium)

• increases hypertension due to reabsorpption of too much net solutes

Aldosterone blocker medication helps with hypotentions or hypertension

Side effect is hyperkalenia

Aldosterone effects on Principal cells of distal tubules

blocks the ENaC (channel on apical membrane) which prevents sodium (Na+) from moving in which prevents potassium from being secreted out into the filtrate

• effects: prevents net solute reabsroption and water reabsroption

• the water and solutes go into the urine

Collecting duct and ADH (testable)

this duct decides how much water you keep based on Aldosterone

• it is the final site where water reabsorption is regulated

• filtrate passes through the medulla (high osmotic gradient) and has the potential to reabsrob water depending on permeability

• permeability depends on aquaporins controlled by high ADH (vasopressin) on the apical membrane

• when ADH targets aquaporins it shifts to the apical/luminal membrane (now water can move thru)

What happens if collecting duct is permeable to water

The water moves out of the filtrate into the hyperosmotic medulla (down gradient)

• increase of water reabsorption, decrease in urine volume

High ADH effects on collecting duct

increase in aquaporins which increase water reabsorption

• leads to a concentrated urine and causes dehydration/high osmolarity

• increases solute reabsorption in AL/DT

• increase diltute filtrate (50 m0ms/L)

low ADH effects on collecting duct

decrease in aquaporins, decreasing water permeability

• water is less reabsorped and so the urine is diluted (overhydration/low osmolarity)

• less solute reabsorption in AL/DT

• resulting in less dilute filtrate (ex: 150 m0sm/L)

Angiotensin II and Aldosterone effects on Collecting duct

it increases Na+ (solute) reabsorption upstream making medulla more concentrated

• this enhances water reabsorption potential in collecting duct

Hypotonic Plasma? (low osmolarity)

Less ADH is releases, meaning less aquporins in collecting duuct

• collecting duct is now impermeable to water

• causes less water reabsorption

FIltrate is dilute which increase urine output (diuresis)

This is bc….

No ADH = no water reabsorption
👉 Water stays in filtrate → excreted as urine

Aldosterone during normal hydration

the baseline is tonic for ADH secretion

• moderate water reabsorption

• normal values of ADH = 1-5 pg/mL

• urine concentration: ~ 300-900 mOsm

How does alcohol affect ADH

It inhibits ADH from the brain by

• decreasing water reabsorption which increases urine output

• this is why u wake up with a headache

Turbulogolmerular feedback

feedback starts in the macula dense cells (distal tubule) and communicates with the afferent arteriole

• too diluted = bad (not enough Na+ delivered downstream)

• later nephrone segments need Na+ to function properly

• Too much salt → constrict (slow down)

• Too little salt → dilate (speed up)

• Works with myogenic mechanism

High NaCl in distal tubule?

Means the filtrate is moving too fast (high GFR)

• afferent arteriole constricts, which decreases glomerular pressure and decreases GFR

Low NaCl in Distal Tubule?

means the filtrate is moving too slow (LOW GFR)

Response:

• afferent arteriole dilates, increase glomerular pressure and increase in GFR

Main components of acid-base balance

• Bicarbonate (HCO₃⁻) = “good” (buffer)

• Hydrogen ions (H⁺) = “acid” (bad)
  → Goal: keep H⁺ low and controlled

CO2​+H2​O↔H2​CO3​↔H++HCO3−​

→ This system allows the body to:

• Convert CO₂ into acid (H⁺)

• Or buffer acid using bicarbonate

Importance of acid regulation

The body produces more acid than base daily

So it must:

• Buffer it (bicarbonate)

• Blow it off (lungs)

• Excrete it (kidneys)

→ “Breathe CO₂, Pee H⁺, Keep HCO₃⁻”

• Lungs → remove CO₂

• Kidneys → remove H⁺

• Bicarbonate → buffers everything