Untitled Flashcards Set

Lecture 20: Key Points
5. The nephron is the functional unit of the kidney. Know that for juxtamedullary nephrons,
certain parts of the nephron (renal corpuscles, proximal tubule, distal tubule) are only
found in the kidney cortex, and that the medulla only contains collecting ducts and loops of
Henle. The renal corpuscle consists of the glomerulus (a tuft of capillaries) inside Bowman’s
capsule. The entire renal tubule is made up of a simple epithelium.
6. Know that blood is brought to the glomerular capillaries by the afferent arteriole and carried
away from the glomerular capillaries by the efferent arteriole. This arrangement increases
the pressure in the glomerular capillaries, which is important for glomerular filtration, as we
will discuss in the next lecture.
7. Understand the basic processes that are performed in the nephron: filtration, reabsorption,
and secretion. Renal handling describes the processes that occur in the nephron for any
particular substance. The amount excreted (rate of excretion) is the sum of these processes:
the filtered load (amount filtered) minus the amount reabsorbed plus the amount secreted
(see slide 27). In the next four lectures we will provide details of the 5 different functions
outlined on slide 28.

Lecture 21: Key Points
1. The filtration membrane consists of the fenestrated endothelium, the glomerular
basement membrane, and the slit diaphragm that spans the filtration slits between the
podocytes. Be able to trace the path of a filtered substance.
2. The filtration membrane forms a barrier that prevents the filtration of protein. Proteinuria
is the hallmark of glomerular disorders. Proteinuria causes damage to the kidney tubules
and loss of nephrons; thus, ongoing proteinuria leads to steadily declining kidney function.
Examples of glomerular disorders are diabetic nephropathy, glomerulonephritis (which
includes the autoimmune disorder lupus), and preeclampsia (slide 15).
3. Filtration is promoted by the hydrostatic pressure in the glomerular capillaries and
opposed by the colloid osmotic pressure and the hydrostatic pressure in Bowman’s space
(slide 17). Glomerular capillary pressure is higher than pressure in a typical capillary
because blood from the glomerulus flows into the efferent arteriole, a high-resistance
vessel.
4. Glomerular filtration rate (GFR) is stable over a wide range of blood pressures due to renal
autoregulation. Renal autoregulation involves feedback mechanisms that are intrinsic to
the kidney, and that act on the afferent arteriole to adjust blood flow and glomerular
capillary pressure. Be able to describe the myogenic response of the afferent arteriole in
renal autoregulation (slide 21).

5. The juxtaglomerular apparatus is a structure that is involved in tubuloglomerular
feedback, the other regulatory mechanism involved in renal autoregulation. The
juxtaglomerular apparatus consists of the macula densa (a sensor) in the distal nephron,
and effector cells in the afferent arteriole (of the same nephron). In tubuloglomerular
feedback, the macula densa senses flow in the distal nephron, and releases paracrine
signals that affect dilation/constriction of the afferent arteriole.
6. GFR is regulated by the sympathetic nervous system (SNS), which innervates the afferent
arteriole. In response to hemorrhage, sensors that monitor blood pressure activate the
SNS input to the afferent arteriole. SNS input causes afferent arteriole constriction and
decreased GFR.
7. GFR is measured by determining the renal clearance of inulin, a plant carbohydrate that is
filtered, but not reabsorbed or secreted. In a routine physical, GFR is estimated using the
measured serum creatinine (see quiz section 5b).

Lecture 22: Key Points
1. Reabsorption is a major process since filtration “throws out” water, ions, and useful
organic molecules. Active transport of Na+ is used to power Na+-linked reabsorption (see
slide 12). Water moves via osmosis, following solute reabsorption.
2. Glucose reabsorption is via secondary active transport in the proximal tubule, and
depends upon the protein SGLT2, which is a target of drugs used to treat diabetes mellitus.
Glucose is normally 100% reabsorbed. In diabetes mellitus, hyperglycemia causes a high
filtered load of glucose, saturating SGLT2 proteins such that glucose ends up in the urine
and increases urine volume (polyuria). SGLT2 inhibitors were shown in post-FDA approval
outcome trials to have favorable effects on cardiovascular and renal disease and are now
approved as treatments for heart failure and chronic kidney disease.
3. The proximal tubule is the site for organic molecule reabsorption and secretion, as well as
some ion reabsorption—all of which depend on active transport requiring ATP. Therefore,
proximal tubule cells are loaded with mitochondria.
4. Proteins involved in Na+ reabsorption are the target of diuretics, drugs that decrease ECF
volume by increasing urine flow. Two key examples are the thiazide diuretics, which
inhibit the Na+/Cl- cotransporter in the distal tubule, and the loop diuretics, which inhibit
the NKCC2 protein in the thick ascending limb of the loop of Henle.

5. The loop of Henle can be divided into two parts: a descending limb and an ascending
limb. The thick ascending limb is so named because it is formed by a simple cuboidal
epithelium, while the rest of the loop of Henle is formed by a simple squamous
epithelium. The Na+/K+/2Cl- cotransporter (NKCC2; target of loop diuretics) is the
protein in the thick ascending limb that actively transports solute out of the tubule and
into the interstitium (slide 23). This active reabsorption of solute is one component
that is involved in the generation of the vertical osmotic gradient in the medulla (see
lecture on Friday).
6. Organic molecule secretion is an active process that occurs in the proximal tubule. The
transporters involved are either coupled transporters or ABC transporters. These
transporters have a broad specificity, and so are subject to competitive inhibition.
We described the example of the drug probenecid, which competitively inhibits
penicillin secretion.
7. We previewed Monday’s topic of water balance by outlining that regulated water
reabsorption occurs in the collecting duct. Vasopressin regulates water permeability
in the collecting duct by regulating the number of aquaporins on the apical membrane
of collecting duct cells.