Lecture 2: An Overview of the Kidney and its Logic Flashcards
What are the functions of the kidney?
- Elimination of Nitrogenous Waste Products
- Regulation of Acid-Base Balance
- Regulation of Blood Pressure
- Regulation of Red Blood Cell Volume (total RBCs in body due to EPO)
- Regulation of Calcium (bone) metabolism
What is filtration pressure?
The pressure that allows fluid to enter the glomerular capillaries
Determined by the following equation:
Filtration Pressure (FP) = GCP – COP –CP
Usually 7mmHg
GCP = Glomerular capillary pressure COP = Colloid Osmotic Pressure CP = Capsule Pressure
What are the forces that favor filtration?
Glomerular capillary pressure
also a capsule osmotic pressure that is mentioned later by Berns
What are the forces oppose filtration?
- Colloid Osmotic Pressure
2. Capsule Pressure aka Hydrostatic Pressure in Bowman’s space
What is oncotic?
Oncotic pressure = colloid osmotic pressure
A form of osmotic pressure exerted by proteins in a blood vessel’s plasma
Oncotic pressure increases as more fluid gets filtered into the glomerular capillaries
-thus increase in protein concentration at end of glomerular capillary means there is a decrease in filtration rate at this area
-this occurs at the Efferent arterioles
How much fluid is filtered by both kidneys combined?
180 liters
What is the ultimate role of glomerular filtration?
Elimination of nitrogenous waste products via
i. urea
ii. uric acid
Utilization of NH3 in urea cycle is key to elimination of the metabolic end product
What are the toxins that the kidney secretes?
- urea
2. uric acid
Where does most of the regulation in kidney occur?
Afferent arteriole
Adjustments in the afferent arteriole will autoregulate renal blood flow and GFR
Kidney tries to keep GFR, filtered sodium load and intrarenal pressures stable
Contains
i. Smooth muscle cell
ii. JGA cells
iii. Sympathetic innervation
What is the function of the juxtaglomerular apparatus?
Get signals from glomerulus about amount of renal blood flow as well as the electrolyte composition
Located on afferent arteriole
What is the proximal tubule?
A “leaky epithelium” that reabsorbs high volumes of fluids and its constituents
Small transepithelial electrical potential
Maintains very small gradients
Has high WATER PERMEABILITY
Transports solute actively and water passively
What is the main driving force of transport
For the proximal tubule?
Gradient for sodium from lumen to cell interior
(140 mEq/L to 20 mEq/L)
Mediated through Na/K ATPase on basolateral membrane
How does water get transported into the proximal tubule?
In two ways
1. Through the cell (and exits out into restricted basal spaces that are slightly hyperosmotic…#2 on picture below)
2. Through tight junctions (#1 because) because Na/K ATPase establishes hyperosmotic solution in the LATERAL INTERCELLULAR SPACE
So the two spaces are the restricted basal spaces and the lateral intercellular spaces
What are the characteristics of distal nephron transport (eg DCT)?
Has a “tight” epithelium
Under hormonal control
Can establish steep gradients with high electrochemical potential
Since it is hormonally regulated, this is where the steady state balance is created
What is ENaC regulated by?
Aldosterone
Why does Na/K ATPase utilize 50% of all cell energy?
Because it is the engine for regulation of cell volume
What is amiloride?
A potassium sparing diuretic
Directly blocks the ENaC in the DCTs, connecting tubules and collecting ducts
Potassium channel still works so that’s why it is “potassium sparing”
Where are aquaporins located?
- Descending LoH
- DCT
- Collecting duct
Other places in body, such as brain
Other places in kidney that is not mentioned
Here
There are 13 types of aquaporins
What is the MoA of ADH?
ADH activates a G-protein coupled receptor
Increases cAMP
Increases Protein Kinase A
Inserts aquaporins into apical membrane
What is the key principle of the organization of renal tubule?
Proximal tubule = bulk reabsorptive system to maintain normal homeostasis
Distal nephron = fine tuning of the body’s content of fluid/minerals
-under control of endocrine systems such as ADH
Where does PCT end?
At the pars recta (straight part of the PCT)
Right before thin descending LoH
How does kidney maintain steady state despite the increasing concentration of solute in the kidney tubules?
Can alter rates and direction of transport
Does so via Synthesis or Destruction of epithelial transporters and changes in morphology
Modulated by hormones
What is the normal sodium urinary excretion?
It “depends”
If there is a lot of sodium, you will need to excrete a lot
If there is not a lot of sodium, you won’t excrete as much
What is relationship between
Excretion and intake? (Lecture takehome point)
Excretion must always be related to intake. If it doesn’t, then you have disease
How does kidney regulate blood pressure?
Can increase circulating volume Can increase vascular resistance Both will increase blood pressure if BP is low Also through the RAAS -renin, angiotensin II, aldosterone
What is Liddle’s Syndrome?
ENaC channel is “stuck” open
Inappropriate high rates of sedum uptake in distal nephron = HTN
Low aldosterone levels because there is defect in ENaC
Key: An example of HTN due to excess extracellular fluid volume
How does the kidney contribute to acid-base balance?
By regulating the amount of buffer base in solution (HCO3-)
pH of 6.8 = coma and death
pH of 7.8 = cramps and death
7.4 = normal
What are the sources of H+?
- Cell metabolism (CO2)
- Food products
- Medications
- Metabolic intermediate byproducts
How do the kidneys respond to acidosis?
Retains bicarbonate ions
Eliminates H+
How do kidneys respond to alkalosis?
Eliminates bicarb
Retains H+
How does Kidney regulate vitamin D synthesis?
Kidney is the main site of formation of 1,25 dihydroxy Vitamine D
1,a hydroxylase is located in the kidney
25,OH-D3 is converted to 1,25 dihydroxy vitamin D due to the actions of 1,a hydroxylase
How does kidney regulate red cell mass?
Through the production of EPO
Oxygen sensor will dictate production rate of EPO
