LECTURE 34 12/2/22 (LECTURE 18 SLIDES: RENAL PHYSIOLOGY CONT.) Flashcards
What receptors will ADH bind to in the kidney?
What receptors will ADH bind to in the systemic circulation?
V2 receptors on principal cells. (07:00)
V1 receptors (07:20)
What do V2 receptors do?
What do V1 receptors do?
V2 receptors help promote water reabsorption.
V1 receptors promote SVR in the systemic circulation (8:11)
Water reabsorption in the collecting duct are dependent on what factor?
Availability of aquaporins to establish water channels.
How many sets of aquaporins channels are there in the collecting ducts?
Three (AQP-2, AQP-3, AQP-4)
Describe the signal transduction cascade when ADH binds with it’s receptor on the kidney.
- ADH binds with V2 receptors on the principle cells.
- This will activate a Gs-GPCR that will activate adenylyl cyclase.
- Adenylyl Cyclase will cyclate ATP to cAMP.
- cAMP will activate Protein Kinase A
- PKA will phosphorylate AQP-2 vesicles that will release AQP-2 water channels to the apical side of the nephron for water reabsorption.
Why do we pee a lot with alcohol?
Ethanol interferes with the release of vasopressin (ADH) from the pituitary gland. (10:26)
What side of the cell will have AQP-2 Channels?
What side of the cell will have AQP-3 Channels?
What side of the cell will have AQP-4 Channels?
AQP-2 (Tubular Side, Apical Side, Luminal Side, or Side with the urine)
AQP-3 and AQP 4 will be on the Interstitial Side
Which AQP channels are not mediated by vasopressin?
AQP-3 and AQP-4
What two neurons does the osmoreceptor communicate with to release ADH?
What other sensor also communicate with these two neurons?
- Supraoptic Neuron
located near the optic nerves - Paraventricular Neuron
located near the 3rd ventricles
The baroreceptors will also communicate with the supraoptic neuron and paraventricular neuron.
(14:30)
The supraoptic neuron is responsible for ________ (fraction) of ADH release.
The Paraventricular neuron is responsible for _________ (fraction) of ADH release.
5/6 of the ADH release for the supraoptic neuron
1/6 of the ADH release for the paraventricular neuron
Where will the supraoptic and paraventricular nuclei send their signal?
What is an alternate name for this structure?
Posterior lobe of the pituitary gland.
Neurohypophysis
What is another name for the anterior lobe of the pituitary gland?
Adenohypophysis (17:40)
What are the names for the urea transporters?
What is the effect of ADH on urea transporters?
UT-A1 and UT-A3
Increase permeability for urea, increasing urea reabsorption.
What are the two reasons to reabsorb urea?
- Reabsorbing urea will increase water reabsorption
- Reabsorbing urea will increase osmolarity of the renal interstitium (21:00)
What happens to the brain as a result of hyponatremia?
Increase brain swelling, due to movement of water into the cell in order to increase osmolarity.
This will also result in increase ICP, decreasing perfusion in the brain.
Will there be a high or low urine osmolarity with less water and urea reabsorption?
There will be a low urine osmolarity (more diluted urine).
In this graph, how many mL of filtrate is reabsorbed in the proximal tubule?
81 mL
(125-44)
In this graph, how many mL of filtrate is reabsorbed with high levels of ADH?
In this graph, how many mL of urine is excreted with low levels of ADH?
124.8 mL of filtrate reabsorbed with high levels of AHD
20 mL of urine excreted with low levels of ADH.
Which of the nephron will have the least ADH effect?
Proximal Tubule
What is the condition where we have too much ADH?
What are the causes of this (4 possibilities) ?
Syndrome of Inappropriate AntiDiuretic Hormone Secretion
(SIADH) - Reduction in urine volume.
- Short response to a brain injury/emergent trauma.
- NSAIDs and pain drugs.
- Antidepressants - SSRIs, SNRIs
- Lung Cancer
(38:00)
If there is a traumatic brain injury with damaged pituitary tissues. What will be the result of ADH?
Decrease ADH and a large amount of urine production.
How does ethanol reduce ADH release from the pituitary gland?
Ethanol reduces calcium influx that generate a current that is required for ADH release at the pituitary gland.
Ethanol will cause a sharp reduction in ADH
(40:00)
How much urine output, would you expect someone to produce if they are on Lithium?
Will the pituitary gland still produce ADH with lithium therapy?
20 L/day
There will still be ADH production, but the kidneys will not respond the hormone.
Differentiate between Central DI and Nephrogenic DI.
Give example for each condition.
Central Diabetes Insipidus: problem releasing ADH in the nervous system. EtOH intake
Nephrogenic Diabetes Insipidus: inability of the kidney to respond to ADH. Lithium intake
Between Central DI and Nephrogenic DI, which one would be easier to treat and how would you treat it?
Central DI would be easier to treat.
Central DI would be treated with Desmopressin or DDAVP.
(44:00)
What receptor is DDAVP more selective on?
What receptor is vasopressin more selective on?
V2 receptors (Increase fluid retention and treat Central DI)
V1 receptors (Increase MAP)
(44:50)
Urea permeability at the collecting duct is dependent on the presence of _____________.
ADH (47:33)
What part of the nephron will you have the most reabsorption of NaCl through active transport?
Proximal Tubule and Thick Ascending Limb
What part of the nephron will water reabsorption be ADH dependent?
Wha part of the nephron will typically have the least reabsorption of water?
Late Distal Tubule
Cortical/Medullary Collecting Duct
Least Water Reabsorption in the Thin and Thick ascending LOH
What would graph look like if ADH and thirst systems were blocked?
Blood osmolarity will not be regulated as tightly with impaired ADH system.
What two hormones will increase thirst?
ADH and ANGII (51:00)
What factors will decrease thirst?
What factors will increase thirst?
What hormone will influence our salt appetite?
ANG II (53:30)
What are factors that can decrease ADH?
What are factors that can increase ADH?
What will be following trends with Addison’s disease?
Aldosterone:
Sodium:
Potassium:
Addison’s disease
Aldosterone: Decrease
Sodium: Decrease
Potassium: Increase
What will be following trends with Conn’s disease?
Aldosterone:
Sodium:
Potassium:
Conn’s disease
Aldosterone: Increase
Sodium: Increase
Potassium: Decrease
How many types of intercalated cells are there? What does each one do?
Type A Intercalated Cells get rid of acid (H+)
Type B Intercalated Cells retain acid (H+)
(76:00)
Which transporters are used in Type A and Type B Intercalated cells for H+ transport.
Type A and Type B cells both use ATP Hydrogen pump and ATP Hydrogen/Potassium exchangers to move H+ ions.
Type A will move H+ to the tubular side.
Type B will move H+ to the interstitial side.
What transporter is used in Type A and Type B intercalated cells for HCO3- transport?
Type A and Type B cells both use Bicarb/Chloride Exchanger.
Type A will move HCO3- to the interstitial side.
Type B will move HCO3- to the tubular side.
Activation of the aldosterone receptor. Does it increase more potassium channels or more sodium channels on the tubular side of the nephron?
Increase in Na+ channels
Verified on 12/7/22
Where are organic cation transporter (OCT) and organic anion transporter (OAT) located?
Proximal Tubule
How are organic cations transported into the nephron lumen?
Two step process:
1. From the interstitium to the cell, they go through organic cation transporter.
2. Once inside the cell, the cation are transported to the tubules by the Hydrogen/Cation+ exchanger.
How does the organic anion transport system work?
(3) Na+/Alpha Ketoglutarate symporter will create an Alpha Ketoglutarate Concentration Gradient.
Anions/ Alpha Ketoglutarate exchanger (sodium dependent antiporters) will move anions into the cell and Alpha Ketoglutarate to the interstitial side of the cell.
Anion is then transported to the tubular side of the cell.
What endogenous compounds are removed through OAT (7)?
Bile Salts
Hippurates
Hydroxybenzoates
Prostaglandins
Oxalate
Urate
Fatty Acids
BHH POUF
What exogenous compounds are removed through OAT (9)?
Furosemide
Saccharin
Salicylates
Sulfonamides
Penicillin
Probenecid
Acetazolamide
Chlorothiazide
Ethancrynate
F SSSPPACE
What endogenous compounds are removed through OCT?
Guanidine
Serotonin
Thiamine
Choline
Histamine
ACh
NE
Creatinine
Epi
Dopamine
GST CHANCED
What exogenous compounds are removed through OCT?
Quinine
Meperidine
Isoprel
Morphine
Procaine
Atropine
Cimetidine
TEA
QM IMPACT
What was used to keep PCN in the system longer during the World Wars?
PAH
PAH looks like endogenous Hippurates
(100:00)
What are the two types of hypertension discussed in class?
Essential hypertension - cause of hypertension is essential unknown, kidneys work at a higher set point
Salt-sensitive hypertension - long term BP is related to salt intake. genetic inherited issue
(108:00)
Does salt intake affect individuals with essential hypertension?
No
Which group of people have high levels of salt sensitive hypertension in their gene pool?
African Americans
Asian Americans
In a healthy individual, how does arterial pressure fluctuate with a high or low salt intake?
Little to no fluctuation in arterial pressure.
How would blocking ANG II and ADH affect arterial pressure in regards to a low sodium intake?
System will have trouble maintaining an adequate arterial pressure, because there is no salt retention system.
How will arterial pressure correlate to a high salt retention system?
Increase arterial pressure with increase salt intake.
(112:00)
How will someone develop a high salt retention system?
Stenosis to one kidney.
The decrease in blood flow will trigger renin release in the stenotic kidney which will cause an increase in ANGII.
ANG II will affect both kidneys, which can result in salt sensitive hypertension.
What are treatments for the high salt retention system caused by a stenotic kidney?
ACE inhibitor
ARB inhibitor
Renin inhibitor
Fix the stenotic kidney
Surgically remove the stenotic kidney
If you remove one kidney what would be your new GFR right after the nephrectomy?
What will be your GFR after 6-12 months?
62.5 cc/min
(125/2)
94 cc/min
The lone kidney will increase its new GFR by 50%
(62.5 x 1.5 = 93.75)
