Exam 1: Lecture 1: Renal Physiology Flashcards
Nephron
Basic unit of the Kidney
Each kidney has about 1 million Nephrons
Efferent arteriole
Moving away
Afferent arteriole
Moving towards
Different cell types in Nephron
Polarized cells (1 side different than other)
Ciliated Cells in PCT = Good SA for absorption
Collecting Duct = Bigger cells, less exchange occurs here
Glomerular Mesangial Cells
Supportive cell of Glomerulus (Immune cells)
Act as phagocytes and remove trapped material from basement membrane of capillaries, make sure not blocked.
Podocytes
Supportive cell of Glomerulus
Structural cells that help maintain structural capillaries
Juxtaglomerular apparatus (JGA)
“Sensor”
Important for regulating blood pressure and flow
Contact point, Made up of two cells
JGA is made up of 2 cell types
Granular cells/Juxtaglomerular cells
Macula Densa Cells
Point of contact
Macula Densa Cells
Portion of Thick Ascending Limb that between afferent and efferent arterioles.
“Detector cells” of flow rate and composition of fluid within Nephron
control GFR and secretion of renin from Granular cells
Granular cells
Secretory cells that secrete Renin
within afferent arterial
What is Renin
Hormone
Controls renal function and sodium balance
Additional Kidney Regulation
Renal circulation
Lymphatics within Kidney
Capsule (Role is to limit swelling)
Renal plasma clearance
Volume of plasma from which a substance is removed from the kidney during a given amount of time
ml/min
Stages of Chronic Kidney Disease
Stages 1-5
GFR and % of Kidney Function decreases as go towards stage 5
4 Main Functions of the Kidney
Filtration
Reabsorption
Secretion
Endocrine (RAAS)
Excretion =
Filtration - Reabsorption + Secretion
Filtration occurs at the level of…..
the Glomerulus and Bowmans Capsule
Proximal Convoluted Tubule water permeability
High
Loop of Henle ( Thin Descending Limb) water permeability
Permeable to water
Loop of Henle ( Thick Ascending Limb) water permeability
nearly impermeable to water
Where does concentration of urine occur?
Loop of Henle
Distal Convoluted Tubule + Collecting Duct water permeability
Variable permeability
“Vital” Reabsorption and Secretion occurs at the….
PCT
“Optional” Reabsorption and Secretion occurs at the…
DCT and Collecting Duct
water goes where….
Na and Cl go
Apical Membrane is the….
Lumenal side
Basal Membrane is the….
Side facing interstitial fluid, capillary space
3 Hormones kidney synthesize and secrete….
Activated Vitamin D3 made in kidney
Erythropoietin
Renin
Activated Vitamin D3 role
promote calcium conservation and increase calcium absorption + reducing calcium loss
Erythropoietin
activates synthesis of red blood cells, increasing blood oxygen capacity.
Negative feedback loop
Kidney release EPO if low O2 in blood.
Renin
enzyme released by JGA in response to a decrease in effective circulating blood volume
Renin-angiotensin system
- Drop in blood pressure or fluid volume (Macula dense cells sense it)
- Renin released from kidney and acts on angiotensinogen (released from kidney) to form angiotensin I
- ACE is released from lungs, and acts on angiotensin I to form angiotensin II
- Angiotensin II acts on adrenal gland to stimulate release of aldosterone.
5a. Aldosterone acts on the kidneys to stimulate reabsorption of salt and water, increasing fluid volume
5b. Angiotensin II also acts directly on blood vessels, stimulating vasoconstriction
Covid-19 and ACE2
Target for the virus is ACE2, where the spike protein binds
ACE2 expressed mostly in the epithelial cells if lungs.
certain drugs or pathologies can increase your expression of ACE2 (ie type I/II diabetes or those taking ACE inhibitors or ARBS, angiotensin II type-1 receptor blockers)
Drugs that can increase ACE2 expression….
Thiazolidindiones and ibuprofen
ARBs
Order of collecting system duct
Glomerulus -> PCT -> Loop of Henle -> DCT -> Collecting tubule -> Collecting duct
Proximal Tubule
** Reabsorption and secretion **
Any damage here will cause alteration in glucose, potassium and other ion levels
Has very high water permeability
Two most important compounds for diuretic action?
Sodium bicarbonate and sodium chloride.
Will have affect on blood volume and water reabsorption
Most important process occurring at PCT is?
Reabsorption
66% of sodium ions 85% of NaHCO3 65% of K+ 60% of water Virtually all glucose and amino acids
Four main transporters of PCT
NHE3
Na/K ATPase
Carbonic anhydrase
Sodium-glucose cotransporter
NHE3
Sodium Hydrogen Exchanger on the Lumen side
Key to how sodium bicarbonate is absorbed
H+ binds to HCO3 to make carbonic acid, and gets converted to H20 and CO2. CO2 will passively diffuse into nephron and turned into carbonic acid via carbonic anhydrase.
Dissociation of carbonic acid, the sodium bicarbonate now gets transported via transporter into interstitial space and towards capillaries.
Na/K ATPase
requires energy and control level of reabsorbed sodium and returning it into interstitial space
Carbonic anhydrase
Bicarbonate reabsorption is dependent on this enzyme
Sodium glucose cotransporter
Responsible for reabsorbing much of glucose that is filtered by the glomeruli
NBCe1-A
transporter that allows HCO3 to exit PCT on basolateral side
Loop of Henle has divided into two parts….
Thick Ascending limb and Thin Descending limb
Thick ascending limb
about 25% of NaCL reabsorbed
thought of as diluting segment, not losing water
NKCC2
Transporter for Na/Cl/K in the Thick ascending limb
ROMK
drives diffusion of K from NKCC2 back into the tubular lumen
this drives transport of Mg and Ca back into blood paracellularly
3 Transporters in Loop of Henle
NKCC2
ROMK
Na/K ATPase
What drives Mg and Ca reabsorption in Loop of Henle?
ROMK channel
Distal convoluted tubule
only about 10% NaCl reabsorbed via NCC (sensitive to thiazide diuretics)
Generally impermeable to water, also diluting function,
Calcium reabsorption under control of parathyroid hormone control.
5 Transporters in DCT
NCC
PTH-Receptor
Na/K-ATPase
Na/Ca exchanger
Ca/H ATPase
NCC transporter
Move sodium and chloride into nephron
Na/K-ATPase
moves sodium back into capillaries
PTH-Receptor
Drive calcium reuptake in DCT
Hormones = transcription factors = slower response by causing up regulation in transporters to bring Ca into cell
Na/Ca exchanger and Ca/H ATPase
Move Ca from Nephron back out into the blood towards capillaries
Collecting Tubule System
Final chance to get back sodium, only about 2-5%
This is the most important site of K+ secretion
Aquaporins being inserted from RAAS occur here
3 important cell types of collecting Tubule system
Principle cells
Alpha/beta intercalated cells
EnaC (Collecting Tubule System, Principle cells)
Brings sodium into cell and makes an electrical potential , not a cotransporter, and drives paracellular transport of Cl into blood towards capillaries.
This also drives secretion of K
Aldosterone (Collecting Tubule System, Principle cells)
Causes increase in ENaC, increasing Na uptake and also increase Na/K ATPase.
This is how it drives Na reuptake and regulate water balance
Intercalated Alpha cells primary secretion of….
proton secretion
H ATPase secrete into Lumen
Intercalated Beta cells primary secretion of….
bicarbonate secretion
H ATPase balances secretion basolateral side
Cl/HCO3 secrete bicarbonate into lumen
Aquaporins of the Collecting Tubule System
Aquaporins are not inserted into the membrane
Vasopression/ADH binds to receptor, causes cAMP mediated insertion of Aquaporins into luminal side of membrane and this promotes the uptake of water. Then Aquaporins on the basolateral side move water into blood.
