What do kidneys regulate? 2

- Blood volume - Blood Pressure

What do kidneys excrete? 2

- Urea, creatinine, bilirubin - Removes foreign chemicals

What does the kidney synthesize? What is the process called? 1

- Glucose via gluconeogenesis

What does the kidney secrete? 3

Hormones - Erythropoietin (EPO) - Renin - Vitamin D

What are the body fluid compartments? 3

1. ICF: intracellular (fluid inside cell) 2. ECF: (fluid outside cell, plasma + interstitial + CSF) 3. Plasma: non-cellular part (fluid inside blood vessels)

What is [water] measured in?

- Osmoles (osm) 1 osm = 1 mol solute particles

T/F: "Low osmolarity" = low water conc

False, it is equal to pure water (aka high water conc)

T/F: The partition between compartments of cell membrane is permeable to just water

False, it is permeable to water AND the solute

What is osmotic pressure?

Pressure necessary to prevent solvent movement

T/F: Osmosis occurs with a selectively permeable membrane

True

How does water flow during osmosis?

High water conc -> low water conc Low solute conc -> high solute conc

What is tonicity?

Concentration of non-penetrating solutes of an extracellular soln relative to intracellular environment

What are the 3 conditions of tonicity?

1. Isotonic: same osmolarity inside and out 2. Hypertonic: higher osmolarity outside the cell 3. Hypotonic: higher osmolarity inside the cell

What is absorption?

Movement of solute/water INTO blood

What is filtration?

Movement of solute/water OUT of blood

What is the formula for Net Filtration Pressure? What are the starling forces?

Capillary Hydrostatic pressure + Interstitial Hydrostatic pressure - Osmotic force due to plasma protein concentration - Osmotic force due to interstitial fluid protein concentration

What does positive net filtration pressure indicate?

Favours filtration

Anatomy of the kidney 3

- Outer cortex - Inner medulla - Nephron

Parts of the nephron 2

- Renal corpuscle - Renal tubule

What is the difference between afferent and efferent arteriole?

Afferent: fluid goes IN Efferent: fluid goes OUT

What is stage 1 of the development of the renal corpuscle?

Nephrons develop as tubules composed of single layer simple epithelium

What is stage 2 of the development of the renal corpuscle?

Capillaries penetrate expanded end of tubules

What are the two other things that happen during stage 2?

- Basal lamina trapped between endothelial cells and epithelial layer - Epithelial layer differentiates into parietal and visceral layer

What is stage 3 of the development of the renal corpuscle? 2

- Parietal layer flattens to become wall of Bowmans capsule - Visceral layer becomes podocyte cell layer

What are the components of the glomerular capillary? 3

- Fenestrated endothelial layer - Basement membrane - Podocytes with filtration slits

Where are all the renal corpuscles found?

The cortex

What are the types of nephrons? 2

- Cortical (major) - Juxtamedullary

What are the functions of the nephrons? 3

- Filtration - Reabsorption - Secretion

What is something the juxtamedullary nephron specially does?

Regulate conc of urine

What are the types of capillaries around the nephron? 3

- Glomerular - Peritubular - Vasa recta

What are the 3 basic renal processes?

1. Glomerular filtration 2. Tubular secretion 3. Tubular reabsorption

What processes get you entry into lumen? 2

- Filtration - Secretion

What processes get you exit out of lumen? 2

- Reabsorption - Excretion of urine

What is the formula for Amount Excreted?

Amount filtered + Amount secreted - Amount reabsorbed

Why are large proteins/albumins held back? 3

- Pore sizes too small - Pores and BM are negatively charges and repel negatively charged proteins - Podocytes have slits that are covered w/ semiporous membranes

What is in the glomerular capillary? 3

- Fenestrated endothelial layer - Basement membrane (BM) - Podocytes w/ filtration slits

T/F: Glomerular filtration is always negative

False, it is always positive

How does GF pressure initiate urine formation?

By forcing protein-free filtrate from plasms out of glomerulus into Bowman's space

What is glomerular filtration rate (GFR)

Volume of fluid filtered from glomerulus into bowmans space per unit time

What factors influence GFR? 4

- Net GF pressure - Neural and endocrine control - Permeability of corpuscular membrane - SA for filtration

Does GFR remain change due to changes in arterial pressure or renal blood flow?

No, it stays constant

How is autoregulation regulated and how does it occur?

- regulated by changes in myogenic reflex - occurs by changing renal blood vessel resistance to compensate for any pressure changes

T/F: resistance changes in renal arterioles alter renal BF and GFR

True

What makes up the juxtaglomerular apparatus (JGA)? 2

- Macula densa - Juxtaglomerular cells (JG)

What is the purpose of the macula densa?

- Cells on wall of distal tubule - Sense increased flow through tubule - Secretes vasoactive compounds - Changes afferent arteriole resistance (paracrine effect) - Signals JG cells

What is the purpose of JG cells?

- On wall of afferent arteriole - Secretes renin

What factors control GFR? 4

- Myogenic reflex - Neuroendocrine input - Paracrine effects - Mesangial cells

What does contraction of mesangial cells cause? 2

- Reduced SA of glomerular capillaries - Reduces GFR

What is the formula for Filtered Load?

GFR x [substance in plasma]

What happens if substance excreted in urine < filtered load?

Reabsorption has occurred

What happens if substance excreted in urine > filtered load?

Secretion has occurred

If only filtration occurs, what substance is being handled? 2

- Inulin - Creatinine

If filtration and partial reabsorption occurs, what substance is being handled? 1

Electrolytes

If filtration and complete reabsorption occurs, what substance is being handled? 2

- Glucose - Amino acids

If filtration and secretion occurs, what substance is being handled? 1

Organic acids

What % reabsorbed is sodium?

99.5

What % reabsorbed is water?

99

What transport/structure is reasborption mediated by? 2

- Diffusion across tight junction (paracellular) -> minor - Mediated transport (transepithelial) -> major

What 2 ways can transepithelial transport occur?

- Across luminal/apical membrane - Across basolateral membrane

T/F: Active T happens on both sides of the membrane for Na+

False, it happens on basolateral membrane by Na/K ATPase

What side of the membrane does passive transport happen?

Apical/luminal side

Where does Na+ reabsorption occur?

Proximal tubule

At normal plasma glucose conc, what is the clearance of glucose?

Zero

How is glucose reabsorbed in the proximal tubule? 2

- Active T on luminal side by - Facilitated diffusion on basolateral side

What protein conducts active T on luminal side?

SGLT

What protein conducts facilitated diffusion on basolateral side?

GLUT (carrier protein)

What is glucosuria?

When its above renal threshold, glucose is in urine - Genetic mutation of Na+/glucose cotransporter

What is the transport maximum?

- Limit of substance that can be transported/unit of time - Binding sites of transport proteins are saturated - Filtered load exceeds limit of reabosorption

Why does glucose appear in the urine with diabetes mellitus?

Capacity to reabsorb is normal, but filtered load increased beyond renal threshold

Is tubular secretion active or passive transport?

Active

What comes from tubular secretion? 3

- Choline - Creatinine - Penicillin

What is renal clearance?

- quantifying kidney function in removing things from plasma

T/F: Inulin is reabsorbed into the body

False, but it is filtered

What is creatinine?

- Product of muscle metabolism

Is creatinine reabsorbed?

No, it is filtered

What happens to X if clearance of X > GFR

X must be secreted

What happens to X if clearance of X < GFR

X must be reabsorbed

If Na+ is actively reabsorbed, is Cl- actively transported?

No, it is passively transported when Na+ is pumped out

How is K+ secreted into tubules? 2

- Distal - Collecting ducts

How does water move across water channels?

- Diffusion - Aquaporins (channel)

Where is water reabsorbed?

Proximal tubule

Are aquaporins open or closed in the proximal tubule?

Open always

Which hormone regulates water reabsorption? 2

- Vasopressin - ADH

What do the water regulating hormones do to the body?

Regulate a type of aquaporin

Where is hormone regulation take place for water?

Collecting ducts

Where does water and salt reabsorption take place in the Loop of henle?

- Water: thin, descending portion - Salt: thick, ascending portion

T/F: the ascending limb is permeable to water

False

What does "counter-current multiplier" mean?

Multiplication of the gradient down the length of the loop of henle

What happens to concentration of fluid inside the tubule when ADH is working?

Fluid becomes isosmotic w/ interstitial space

T/F: more water is absorbed from cortical collecting tube due to ADH

True

What is the effect of the high osmolarity gradient established in the interstitial space?

Helps water permeate out of medullary collecting tubule

How does vasa recta help countercurrent exchange? 3

- BF is VR serves as countercurrent exchangers - BF in medulla is low - Capillaries are permeable to ions, urea, water and can move in/out in response to conc gradient

Does the VR create medullary hyperosmolarity?

No, but it prevents is from being washed out = maintaining it

Where is 50% of urea reabsorbed and secreted?

- Reabsorbed: proximal tubule - Secreted: back into loop of henle

When 100% of urea enters distal tubule, how much gets reabsorbed, and where?

30% reabsorbed in cortical collecting duct

What does minimal uptake of urea by the VR and recycling urea in interstitial space cause?

Maintain high osmolarity in medulla

What is the mechanism to maintain hyperosmotic environment of medulla?

1. Counter-current anatomy/opposing flow through LoH of nephrons 2. Reabsorption of NaCl in ascending limb 3. Impermeability of ascending limb to water 4. Trapping of urea in medulla 5. Hairpin loops of VR maintain hyperosmotic interstitium in medulla

What is vasopressin (aka ADH)?

- Peptide hormone

What is the mechanism for vasopressin release? 4

- Osmoreceptors sense increase is plasma osmolarity - Sense reduction in plasma volume - Produced by cells of the SON of hypothalamus - Secreted from posterior pituitary

What happens to the collecting ducts when there is an absence of ADH?

They become impermeable to water = Pee a lot = water diuresis

What is central diabetes insipidus?

Failure to release ADH

ADH increase means? what environmental factors cause this?

- Pee less - Shock, pain, warm, water deprivation

ADH decrease means? what environmental factors cause this?

- Pee more - cold, humid, alcohol

What is osmotic diuresis? what disease is it associated with?

- Excess solute in urine w/ high water secretion - Diabetes mellitus

T/F: Na is never secreted into renal tubules?

True

What are the short term effects of low conc of Na in plasma?

Baroreceptors regulate GFR

What are the long term effects of low conc of Na in plasma?

Aldosterone facilitate Na reabsorption

What hormones are needed for aldosterone secretion? 2

- Renin - Angiotensin II

What are the effects of high conc of Na in plasma? 3

- ANP (peptide) - ANP regulated GFR and stops Na reabsorption - ANP works by inhibiting aldosterone effects

Where are baroreceptors located? 4

- Carotid sinus - Aortic arch - Major veins - Intrarenal (JG of JGA)

Where is baroreceptor info processed?

Medulla oblongata

Baroreceptors: what does an increase/decrease in BP cause?

Increase/decrease in stretch = increase/decrease in nerve impulse frequency

Where is the site of aldosterone action?

Late distal tube and cortical collecting duct

What are the aldosterone actions? 3

- Induce synthesis of Na transport proteins - Stimulate Na reabsorption - Reduce Na secretion

What does high Na intake do to aldosterone?

Low secretion

What type of stimulus does the renin-angiotensin system respond to? 3

- Sympathetic stimulation of renal nerves - Decrease in filtrate osmolarity - Decreased BP

What does increased stretch mean for renin?

Inhibit release

T/F: JGA cells secrete renin?

True

T/F: macula densa senses NaCL load of filtrate?

True

What are the 3 inputs that the JG cells receive to determine conc of renin?

- Sympathetic input from external baroreceptors - Intrarenal baroreceptors - Signals from macula densa

Where is ANP made?

Cardiac atria

What are the effects of ANP? 3

- Inhibit aldosterone - Inhibit Na reabsorption - Increase GFR and NA excretion

What stimulates ANP secretion? 3

- Increased Na - Increased BV - Atrial distention

Where is K reabsorbed? 2

- Proximal tubule - Loop of henle

Hyperkalemia

Excess K in blood

What is the pH for ECF?

7.35 to 7.45

What is it called when plasma pH < 7.35

Acidosis

What is it called when plasma pH > 7.45

Alkalosis

What pH levels are fatal?

- pH < 6.8 - pH > 7.8

What are nonvolatile acids? examples?

- Organic/inorganic acids from other sources than CO2 - Phosphoric acids, sulfuric acids

What is a buffer?

Any substance that binds to H+ - Made of weak acid and CB - Modify change in pH after addition of acids or bases Buffer + H+ -> HBuffer

What is the extracellular buffer system?

CO2/HCO3

What is the intracellular buffer system?

Phophate ions and proteins - Hb

What are the kidneys and lungs both responsible for?

Balancing H+ conc within narrow range

What causes H+ imbalance? Respiratory 3

- Hyperventilation - Hypoventilation - Resp malfunction

T/F: an increase in H+ conc inhibits ventilation

False, it stimulates ventilation

Kidneys or lungs: which is short-term role?

Lungs

Is reabsorption of HCO3 active or passive?

Active

Where does HCO3 reabsorption occur? 3

In proximal tubule, ascending loop of henle, cortical collecting duct

What happens when more H+ secreted than HCO3 in lumen to bind the H+? 3

- Extra H+ binds to HPO4 - HCO3 generated by tubular cells and diffuses into plasma - NET gain of HCO3 in plasma

Mechanism of HCO3 addition to plasma 4

- Uptake of glutamine from glomerular filtrate or peritubular plasma - NH4 and HCO3 formed inside cells - NH4 actively secreted via Na/NH4 counter transport into lumen - HCO3 added to plasma

How do kidneys compensate during resp acidosis?

- Secreting H+ and lowering plasma H+

How do kidneys compensate during resp alkalosis?

- Excreting HCO3

Metabolic acidosis

- Diarrhea - Diabetes mellitus - Results in increased ventilation - Results in increased H+ secretion

Metabolic alkalosis

- Occurs after prolonged vomiting - Results in decreased ventilation - Results in increased HCO3 excretion