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Renal Physiology
The kidneys 5 functions
1) Regulation of body fluid volume
2) Regulation of Osmolarity & Ion Balance
3) Regulation of pH
4) Excretion of Wastes
5) Synthesis of Hormones
Kidney Anatomy
Blood enter/leaves via Renal artery/vein
Urine leaves via Ureter
Nephron
Nephron: 4 ways substances move
Blood
Filtrate
Urine
Filtration
Bowman’s Capsule
Efferent
Arteriole
Podocyte
Glomerulus
Proximal tubule
Glomerular
capillary
Afferent
Arteriole
~ 20% PLASMA entering Glomerulus enter NEPHRON by BULK FLOW!
What is filtered?
VIDEO
Filtrate in Nephron contains Plasma (ions, waters, small molecules)
It SHOULD NOT contain large proteins or blood cells (they can’t fit through Pores/Slits)
How much is filtered?
Normal: 125 ml/Min = 180 L/day =
Glomerular Filtration Rate
Your plasma is filtered 60 times per day!
Blood flow to kidney MUST be HIGH
Control of Filtration Rate
Local mechanisms alter the diameter of the afferent arteriole
Bowman’s Capsule
Efferent
Arteriole
Podocyte
Macula Densa
(Ascending LOH)
Glomerulus
Proximal tubule
Glomerular
capillary
Afferent
Arteriole
Macula Densa releases local control chemicals (ATP, ADP, NO)
Control of Filtration Rate
Sympathetic ANS: vasoconstriction of afferent & efferent arterioles
REDUCED FLOW, decreased Filt. Rate
Hormones: Angiotensin II > vasoconstriction > decreased Filt. Rate
Prostaglandins > vasodilation > increased Filt. Rate
Angiotensin II & Prostoglandins also
affect the size of the filtration slits!
Reabsorption: What is reabsorbed?
99% of molecules entering renal tubule are reabsorbed into peritubular capillaries!
Na+, K+, Ca2+, Glucose, Water, Cl-, Urea, small proteins
Reabsorption
Active Transport of Na+ DRIVES REABSORPTION!!!!!!!
Everything else is DIFFUSION (electrical or concentration gradient)
Na+ reabsorbed by
Active Transport!
Na+ Electrical Gradient
Anions (-) reabsorbed
Na+
Anions
hypertonic
Osmotic gradient (high ISF)
Water reabsorbed
Water
High Renal Tubule Conc.
Ca2+
K+
Urea
Renal Tubule
Other molecule diffuse
down conc. gradients
ISF
Glucose Reabsorption
100% of Glucose is reabsorbed @ normal blood glucose levels
Diabetes mellitus > elevated blood glucose >> glucosuria
Secretion
FROM Peritubular Capillary TO Renal Tubule
Organic molecules (too big for Filtration), K+, H+ are key molecules SECRETED
Penicillin (Antibiotic) Secretion
Penicillin is filtered & secreted
@ 4 hours: plasma conc. of penicillin = 0
100% of Penicillin is EXCRETED by 4 hours
Excretion
Water
Glucose
180 L/Day
-
178.5 L/Day +
200 mg/min - 200 mg /min +
0
0
=
=
1.5 L/Day
0 mg/min
Fluid and Electrolyte Balance
Why does your body maintain fluids and electrolytes in a balanced state?
Na+ & Water determine blood volume and pressure
K+ is essential for resting membrane potential in excitable cells
H+ and HCO3- are key in maintaining pH
Ca2+ is a key signaling ion
Integrative, multisystem task; kidney, cardiovascular, respiratory, neural
Water Homeostasis
8 – 8oz waters
9 oz from food
Living in DRY Places
can INCREASE
Diarrhea can INCREASE
You body maintains water homeostasis, PRIMARILY, by altering urine volume!
Water Reabsorption
Important: Water reabsorption in the LOH is ALWAYS on (unless drugs are present)
Your body ONLY alters water reabsorption in the distal tubule & collecting duct!
Variable Water Reabsorption
Vasopressin (ADH) & Aquaporins
Antidiuresis = little concentrated urine
Antidiuretic Hormone (ADH) = Vasopressin
Vasopressin (ADH) & Aquaporins
Diuresis = lotsa dilute urine
What drives ADH release?
1) Blood Osmolarity
High OSM > Increase ADH
Low OSM > Decrease ADH
2) Blood Volume
3) Blood Pressure
Low BP> Increase ADH
High BP> Decrease ADH
Sodium Homeostasis
Na+ balance is intimately tied to blood pressure and volume homeostasis!
25% of Adult Americans are Hypertensive
Hypertension = Leading Cause of Cardiovascular Death!
Excess SALT Intake is Major contributing Factor
Americans consume : 3.5 - 8 grams per day
NAS recommended: 2 grams per day
Effect of ingested Sodium on Kidney Function
ASSUME: Each day you consume 2 grams of salt
This could increase you blood osmolarity to 307 mosm/L
Cardiovascular
Atrial natriuretic peptide
(ANP)
Aldosterone Pathway
Renal =
Renin-Angiotensin-Aldosterone Pathway
Aldosterone: Adrenal hormone that regulates Na+ reabsorption
Aldosterone : more Na-K ATPase pumps
more K+ and Na+ channels
Sodium Reabsoption is
variable ONLY in the
distal tubule and
collecting duct
Aldosterone Release controlled by Osmolarity
Adrenal Cortex
Reduce Aldosterone
Synthesis
Sodium Excretion
Aldosterone Release is also controlled by Blood pressure
Renin-Angiotensin-Aldosterone Pathway
constantly
produces
Liver
Angiotensinogen
in the plasma
produce
Low Blood Pressure
Kidney
ANG I in plasma
contains
Blood vessel
endothelium
Vasoconstrict
ACE
(enzyme)
ANG II in
plasma
Sympathetic
Activation
Heart
Vasculature
Renin
Hypothalamus
ADH
Synthesis
Water Reabsorption
Increase Blood Pressure
Thirst
Adrenal Cortex
Aldosterone
Synthesis
enhances Sodium Reabsorption
Increase Blood Volume
Aldosterone Release controlled by Osmolarity
Adrenal Cortex
Reduce Aldosterone
Synthesis
Sodium Excretion
Aldosterone Release is also controlled by Blood pressure
Renin-Angiotensin-Aldosterone Pathway
constantly
produces
Liver
Angiotensinogen
in the plasma
ACE inhibitor
produce
High Blood Pressure
Renin
drug for HYPERTENSION
Kidney
ANG I in plasma
contains
Blood vessel
endothelium
ANG II in
plasma
Sympathetic
Activation
Vasodilation
Heart
Vasculature
ACE
(enzyme)
Hypothalamus
Reduce ADH
Synthesis
Water Excretion
Lower Blood Pressure
Thirst
enhances
Adrenal Cortex
Reduce Aldosterone
Synthesis
Sodium Excretion
Reduce Blood Volume
Adrenal Cortex
Reduce Aldosterone
Synthesis
Cardiovascular
Reduce ANG II
Sodium Excretion
Atrial Natiuretic Peptide (ANP)
BP
Blood Volume
Atrial
Stretch
ANP secretion
Decreased ADH
Increase
GFR
Decreased
Renin
Increase Water Excretion
Lower Blood Volume
Decreased
Aldosterone
Decreased
Sympathetic
Increase Na+ Excretion
Lower Blood Pressure
General Pathways for Sodium, Blood Volume, and Blood Pressure Homeostasis
Adrenal Cortex
Increase ANP
Decrease Symp.
Reduce Aldosterone
Synthesis
Reduce ANG II
Sodium Excretion
pH Review
More H+ ions
Few H+ ions
Acid-Base Homeostasis: pH
pH is affected by the concentration of H+
Your body maintains pH at 7.38-7.43, precisely!
Low pH = acidosis (reduced CNS function)
High pH = alkalosis…hyperexcitable membranes
(diaphragm arrest!)
Where do acids (H+ ions) come from?
H+ is always being produced
….so…
H+ always needs to be excreted
3 mechanisms of pH homeostasis
1)
Buffering systems
75%
2)
Lungs
3)
Kidneys – 25%
Loss of any mechanism can lead to ACIDOSIS > lowered blood pH
The buffer of H+ is HCO3CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3Law of Mass Action
CO2 + H2O
H2CO3
H+ + HCO3-
H+ combines with HCO3- to BUFFER the effect of increase H+
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3More CO2 & H2O are produced by buffering action
HCO3- is used up
HCO3- is 600,000 x more concentrated than H+ in blood
Respiratory Regulation of pH
CO2 + H2O ← H2CO3 ← H+ + HCO3Brainstem chemoreceptors
Carotid & Aortic
chemoreceptors
Increased Ventilation Rate and Volume
CO2 + H2O → H2CO3 → H+ + HCO3-
Renal Regulation of pH- 25%
1)
Reabsorbtion of HCO3- ; indirect excretion of H+
Filtered HCO3- cannot be directly reabsorbed
Hydrogen
Phosphate Ion
HPO42-
HCO3-
Most Filtered H+ is not directly excreted
H+
H+
Always ON
HCO3-
ATPase
REABSORBTION
HCO3-
H2CO3
H2CO3
C.A.
C.A.
H2O + CO2
H2O + CO2
REABSORBTION
H2PO4Phosporic Acid
NH4+
Ammonium Ion
PROXIMAL
Renal Tubule
NH3
Amino
Acids
Nephron
Cell
HCO3-
HCO3-
Renal ISF
Peritubular
Capillaries
Skeletal System: Functions
1) Support
2) Movement
3) Calcium Homeostasis!
Parathyroid Gland
Ca2+ receptors are linked to G-protiens that control
the release of PTH (parathyroid hormone)!
Calcium Homeostasis
Ca2+ Receptors in Parathyroid gland
monitor blood Ca2+ levels
1) If Ca2+ Low – PTH released
Bone breaks down releasing Ca2+
Kidney reabsorbs Ca2+
Intestines uptake more Ca2+
2) If Ca2+ High – PTH syn. inhibited
Bone building, incorporating Ca2+
Kidney does not reabsorb Ca2+
Intestines do not uptake Ca2+
Bone accounts for 99% of the calcium reserves in your body!
Osteoporosis
Osteoporosis is linked to long-term
low dietary intake of Ca2+
Bone Loss > Bone Building…
so that Ca2+ levels are maintained
Ca2+ is a key ion everywhere!!!!
Women are more susceptible than men….lower bone mass & menopausal estrogen decrease