3 - Renal Physiology Review Flashcards
What is the central physiologic role of the kidneys?
To control the volume and conposition of body fluids.
What is the distribution of body fluids in the intercellular fluid and extracellular fluid? What does this tell us about the avg 70 kg man?
ICF = 2/3 of total body water (40% of body weight)
ECF = 1/3 of total body water (20% of body weight)
Avg 70kg man with ~42 L of TBW would have ~28 L (42 x 2/3) in the ICF and ~14 L (42 x 1/3) in the ECF.
The barrier between these compartments is the cell membrane.
What are the major anions and cations in the ECF and ICF?
ECF: Na+ and Cl-
ICF: K+ and phosphates and proteins
What is the distribution of water between the ECF and ICF governed by?
Osmotic forces.
What is osmolarity? How do they differ in the ICF and ECF of the body? What is osmolality?
Osmolarity: The concentration of osmotically active particles in total solution and is expressed in mOsm/L water
In the body, the osmolarity of the ECF and ICF averages 280-300 mOsm/L and it is nearly identical in all major compartments of body fluids.
Osmolality: expressed in mOsm/Kg solvent (water), in relaticely dilute solutions such as the body, osmolality=osmolarity.
What is the effect of adding isotonic, hypertonic, and hypotonic solutions to the ECF?
What are the four processes of the kidney that determine the composition of the urine?
- Filtration
- Reabsorption
- Secretion
- Excretion
Excretion = filtration - reabsorption + secretion
What is the glomerular filtrate? What does the fluid contain?
An ultrafiltrate of plasma formed by the net effect of starling forces to more (filter) fluid out of the glomerular capillaries and into bowman’s space.
- contains same concentration of most salts and organic substances found in plasma
- most large proteins, substances bound to protein, and cellular elements are excluded from the glomerular filtrate
- its a bulk processes; the 70kg man will filter his entire plasma volume (~3L) every half hour.
What are the physical forces that cause filtration by glomerular capillaries?
Glomerular hydrostatic pressure pushes blood into bowmans capsule; this force is opposed by bowman’s capsule pressure and glomerular colloid ostmotic pressure.
Since glomerular hydrostatic pressure is so high (60 mmHg) the other two forces are not enough to overcome it and the net effect is FILTRATION with a pressure of 10 mmHg.
What is the rate of flow in the afferent arteriole, the glomerulus, and the effeerent arteriole?
Afferent arteriole: renal plasma flow = 700 ml/min
GFR = 125 ml/min
Efferent plasma flow (EffPF) = 575 ml/min
What are the two mechanisms of GFR and RBF autoregulation?
Myogenic mechanism: intrinsic property of vessels. Stretch of vascular smooth muscle, as experienced during increased art pressure, elicits contraction which elevates vascular resistance and maintains blood flow and GFR constant.
Tubuloglomerular feedback: in response to an elevation in perfusion pressure, increase fluid is filtered leading to increased delivery of NaCl to the macula densa. This increased delivery elicits an increase in vascular resistance.
What is the structure of the juxtaglomerular apparatus?
The macula densa sits near the vascular pole, between the efferent and afferent arteriole.
It has a specialized population of cells that sense how much sodium is delivered to this part of the nephron. When they see too much sodium, it will send a signal to afferent arteriole (JG cells) to tell them to constrict to decrease RBF to glomerulus. The efferent arteriole would also respond.
Describe the feedback from the macula densa?
- Decrease in arterial pressure causes a decrease in glomerular hydrostatic pressure and initial (transient!) decrease in GFR.
- When the macula densa sees lower amount of sodium, it signals to the JG cells and afferent arteriole and tells afferent to relax and let more blood in.
- Renin release is stimulated to cause the efferent arteriole to vasocontrict (increase resistance) to make it harder for blood to leave glomerular capillary.
- Both of these changes make blood higher in the glomerular capillary.
What hormones and autocoids decrease GFR?
- Norepinephrine
- Epinephrine
- Endothelin
- Angiotensin II (no change or decrease)
What hormones and autocoids increase GFR?
Endothelial derived nitric oxide
Prostaglandins
What are the componants of the glomerular filtration barrier?
Capillary wall: with 700 Å fenestrations that are freely permeably to small molecules. Negatively charged glycoproteins in surface.
Basement membrane: porous matrix of EC proteins including type IV collagen, laminin, fibronectin, and other negatively charged proteins.
Podocytes with processes and slit pores 40x140 Å. Long finger-like processes with negatively charged proteins.
How does the glomerular filtration barrier select things to pass through?
Size selective: more permeable to small molecules
Charge-selective: more permeable to positively charged molecules (proteins are generally negatively charged)
What are the components of the podocytes of the filtration barrier?
The foot processes contain a contractile system linked to the slit diaphragm components nephrin (N) and P-cadherin (P-C).
This changes how tight the foot processes are and how slective they are.
What is the function of hte proximal tubule? What diuretic works here?
Reabsorbs 65% of the filtered sodium, chloride, bicarb, and potassium and essentially all filtered glucose and amino acids.
Secretes organic acids, bases, and H+.
Carbonic anhydrase inhibitors (acetazolamide) inhibits H+ secretion and HCO3- reabsorption. Since H+ secretion is coupled to Na+ reabsorption, you get less Na+ reabsorbed and thus have a diuretic effect.
How does the osmolarity, Na+, HCO3-, glucose, and amino acid concentrations change as fluid moves through the proximal tubule?
The reabsorption is isosmotic - which means that osmolarity stays the same.
Creatinine is filtered but not reabsorbed so it increases in concentration.
Bicard is reabsorbed so it decreases in concentration.
Glucose and amino acids are almost completely reabsorbed so they decrease greatly in concentration.
What type of absorption occurs in the thin descending loop of henle?
Reabsorption of water secondary to cortical-medullary osmotic gradient.
This concentrates the filtrate.
Describe the reabsorption in the thin ascending loop of henle?
It’s impermeable to water; passive reabsorption of sodium dilutes the tubular fluid.
Permeable to urea, urea is secreted.
What is absorbed in the thick ascending look of henle?
Reabsorbs 25% of filtered Na by the Na/K/2Cl transporter.
Lumen positive potential drives paracellular reabsorption of sodium, potassium, magnesium, and calcium.
Impermeable to water, dilutes tubular fluid.
What are the transport characteristics of the early distal tubule? What drugs is it sensitive to?
Reabsorbs Na, Cl-, Ca2+, and Mg2+
Not permeable to water.
Thiazide sensitive segment.
What is the MOA of thiazide diuretics and where does this occur?
Inhibits the NaCl symporter in the early distal tubule.
What are the transport characteristics of the principal cells of the late distal tubule and cortical collecting duct? What are they regulated by?
Reabsorb Na+ and secrete K.
Regulated by aldosterone.
Water permeability regulated by ADH.
What RAA and diuretics work on the principal cells of the late distal tubule and cortical collecting duct?
Na channel blockers: amiloride and triamterene block the sodium channel on the apical membrane of the principal cells called the ENaC channel.
Aldosterone antagonists: spironolactone nad eplerenone
What are the transport characteristics of the medullary collecting duct?
Reabsorbs Na+ (similar to principal cells)
ADH-stimulated water reabsorption
Urea reabsorption in the medullary CD.
Increaseing renal perfusion pressure from 100-130 will most likely cause an increase in what? Why is this? How does acute kidney injury change this?
Urine flow rate.
Normal variation in blood pressure, the blue (renal blood flow) and red (GFR) curves don’t change much. Green curve (urine output) increases with blood pressure.
Acute kidney injury from ischemia takes you out of normal range of RBF and causes the perfusion pressure to drop below the normal range and that’s when you have a decrease in GFR. This can cause acute kidney failure from ischemia.
