Basic Renal Structure and Functions week 1 Flashcards
Why are the kidneys overperfused? What does it mean for them to be overperfused?
Kidneys are <1% of body weight but use ~7% of all oxygen used in body. Thus the kidneys are overperfused-receive substantially more blood flow than is is needed to meet their metabolic demands. This high O2 consumption is due to the huge amount of energy used by the numerous active membrane transport processes in the kidney. Kidneys receive about 20-25% of the cardiac output. For comparison…..Brain gets ~13% …..Heart gets ~4% Point here is that kidneys receive much more blood flow than they need to stay alive. Thus, the high blood flow accomplishes something else.
What are the 2 major fxns of the kidney? (just list)
1) Maintenance of a Relatively Constant Extracellular Fluid Composition
2) Generation of Hormones
In what ways does the kidney maintain a relatively constant extracellular environment?
List and describe the specific sub-functions of the kidney that contribute to this function.
A very important role of the kidney is maintaining the relatively constant extracellular environment that is necessary for normal cellular function. This is accomplished by the excretion in urine of many waste products of metabolism (e.g., urea, creatinine) as well as any excess water and solutes that arise from dietary intake. In short, kidneys adjust the content and volume of urine as dietary and metabolic challenges arise in order to keep the extracellular environment relatively constant. This is accomplished not only by moving substances into the fluid that will become urine (i.e. secretion) but also by moving substances out of this fluid (i.e. reabsorption).
Sub-functions of maintenance of constant extracelluar environment:
- Regulation of plasma H20 and electrolyte levels
- Control of plasma osmolarity
- Elimination of many metabolic waste products
- Ridding body of abnormal substances (e.g. drugs, antibiotics, pyrogens, etc.)
- Regulation of normal acid/base balance
- Modulation of blood pressure
1a. Regulation of water & electrolyte composition of the blood. A major pathway out of the body for extra ingested water and salt is via the kidney. Over time, it is obviously important that total body water as well as the concentrations of salts (like NaCl and other important electrolytes) are maintained essentially constant. This means that intake and output from the body must be equal. Typical salt intake per day is about 10 grams and water intake is roughly 2.5 L. Some of this may be output from the body via the GI tract, lungs and/or skin (via sweating). However, the kidney is responsible for ~95% of all salt output and normally about 60% of water output.
1b. Control of blood osmolality. The osmolality of the plasma is primarily (but of course, not exclusively) determined by the concentration of NaCl. The kidney can control NaCl and water levels in the urine independently. This ability is used to regulate plasma osmolality by adjusting total body water & salt content. Note: Osmolality is somewhat different than osmolarity. Osmolarity is the amount in moles of osmotic particles per liter of solution. In contrast, osmolality is the amount in moles of osmotic particles per kilogram of water. In most physiological circumstances, the osmolarity or osmolality of a solution are usually similar values. Osmolality is slightly higher because the space occupied by solutes means that more than 1 liter of a solute-containing solution is needed for it to have 1 kilogram of water.
1c. Elimination of many metabolic waste products from blood. Numerous waste products are formed as the result of the body’s metabolism. For example, urea results from the breakdown of proteins. Uric acid is formed from the breakdown of nucleic acids. These substances can be toxic if high enough levels are allowed to accumulate in the body. High blood urea is called uremia. High uric acid levels result in gout. The kidney removes these and many other metabolic waste products from the body.
Elimination of other substances from blood (such as exogenous drugs). Many drugs are eliminated from the body in urine. The rate of elimination can vary a great deal. For example, penicillin must be given frequently to overcome its rapid loss in urine. Pyrogens are proteins released during various illnesses that lead to an elevation of body temperature (fever). The level of these pyrogens can be reduced in the blood by increasing urine flow rate (accomplished by drinking lots of fluids). 1e. Regulation of normal acid-base balance (i.e., blood pH). Maintenance of blood pH within a relatively narrow range (centered at pH ~7.4) is vital to normal cellular function. The body typically has to eliminate about 60 mEq of “fixed” H+ each day. Urine is normally acidic, but most of the H+ ingested or produced by metabolism is counteracted by the addition of bicarbonate (HCO3 - ) to the blood by the kidney. Bicarbonate gain is equivalent to H+ loss (more about this later). Many conditions/illnesses result in acid-base imbalances that can be compensated by the kidney (provided the kidney is not the cause of the problem). Renal pH compensation is a relatively slow process (again more about this later).
1.f. Regulation of blood pressure. The kidneys can, over time, regulate blood volume by changing overall body water content. Increased blood volume increases central venous pressure, venous return and hence cardiac output.
Describe the hormones and the function of hormones produced by the kidney.
2a. Hormonal regulation of blood pressure. The kidney secretes renin which alters blood pressure by increasing levels of angiotensin II in the blood. Angiotensin II is a vasoconstrictor. This will be covered in greater detail later.
2b. Stimulation of the production/maturation of red blood cells (RBCs). Low blood O2 levels triggers production of erythropoietin by interstitial cells in the renal cortex. Erythropoietin stimulates RBC precursor cells in bone marrow to mature. A synthetic erythropoietin is now available and can be used to counter anemia (low RBC number). Synthetic erythropoietin has also been abused as a “blood doping agent” to improve athletic performance with possible side effects including blood “thickening”, heart attack and/or an immune response.
2c. Production of the active form of vitamin D (calcitriol). Vitamin D is produced in the skin and is present in the diet. It is converted into its active form (calcitriol) by two hydroxilation reactions. One of these reactions occurs in the kidney (the other occurs in the liver). Calcitriol, a potent steroid hormone, promotes Ca2+ absorption in the GI tract. It is therefore vital in maintaining normal plasma Ca2+ concentration. Vitamin D and/or calcitriol deficit can lead to the disease “Rickets” (which is characterized by soft bones) or promote osteoporosis (which is characterized by fragile bones).
What are the miscellaneous other functions of the kidney?
Miscellaneous Other Functions
Gluconeogenisis: synthesis of glucose
Catabolism of small peptide hormones (Ang. II, ADH, insulin, etc.)
Point: Kidneys do much more than just filter waste from blood:
Keep “balance” of numerous substances
Regulate of osmolarity, blood pressure, acid/base status Generate renin, erythropoietin & help generate calcitriol Catabolism of peptide hormones
Gluconeogenisis
Gross structure of the kidney: Explain the gross structure of the kidney. What structures contain smooth muscle and why? Define the following terms:
cortex
medulla (what is contained within the cortex and medulla)
nephrons
renal pyramids
papilla
minor calyx
major calyx
renal pelvis
ureter
bladder
The major gross anatomical features of the human kidney are illustrated in Figure 1.1 (attached). The kidney consists of an outer cortex surrounding by a central region called the medulla (the medulla is further divided into the inner and outer medulla). The cortex and medulla contain nephrons (the functional units of the kidney), blood vessels, lymphatics and nerves. The human kidney is divided into 8 to 18 conical regions called renal pyramids. The apex (point) of each pyramid is called a papilla and projects into a minor calyx. The calyces act as collecting cups for the urine formed by the renal tissue in the pyramids. The minor calyces empty into two or three pouches called major calyces. These in turn empty into the renal pelvis which is connected to the ureter. The walls of the calyces, pelvis and ureter contain smooth muscle which contracts to help propel urine toward the bladder.
About how many nephrons does each kidney have?
What are the parts of each nephron?
What is a renal corpuscle? What is the function of a renal corpuscle?
Where do reabsorption and secretion occur? What is the end product of nephrons?
T or F: Each nephron has its own collecting duct.
Figure 1.2 (attached) shows the basic structure of the nephron. Each kidney has about 1.2 million nephrons. Each nephron consists of a glomerulus, Bowman’s capsule, proximal tubule, loop of Henle, distal tubule and collecting duct. Multiple nephrons may share a collecting duct. Together, a glomerulus and a Bowman’s capsule are called a renal corpuscle. The renal corpuscle is the site where the filtration of blood occurs. The filtered fluid (or tubular fluid) enters the Bowman’s capsule and progresses through the rest of the nephron. Reabsorption/secretion of various substances (from/to the tubular fluid) takes place as it passes through the nephron. The end product is urine, which is ultimately excreted from the body. The nephron will be discribed in greater detail shortly.
Explain renal circulation beginning with the renal artery.
The renal artery enters the kidney alongside the ureter, branching to become the interlobar arteries. These in turn give rise to the arcuate (or arciform) arteries, which finally lead to interlobular arteries. These branch and radiate toward the renal corpuscles in the renal cortex. The artery narrows to form the afferent arteriole just before reaching the renal corpuscle. Afferent arterioles branch, forming a “ball” of glomerular capillaries (or glomerulus, one per nephron). The parallel arrangement of blood flow (one interlobular artery eventually feeding many individual glomeruli) means that changes in local flow in one glomerulus will not substantially affect overall flow to all the neighboring glomeruli. Each set of glomerular capillaries coalesce to form an efferent arteriole which carries blood to a second capillary bed called the peritubular capillaries.
Explain the differences btwn the 2 types of nephrons.
How are their peritubular capillaries different?
As shown in Figure 1.4 (attached), there are two kinds of nephrons (cortical & juxtamedullary) and the arrangement of their peritubular capillaries is different. Cortical nephrons (sometimes called superficial nephrons) arise high in the cortex and have loops of Henle that do not reach the inner medulla. Juxtamedullary nephrons also arise in the cortex (but near the cortex-medulla border) and have loops of Henle that extend into the inner medulla. The long loops of Henle of juxtamedullary nephrons are associated with a particular type of peritubular capillary called the vasa recta. The vasa recta have an extended loop-like structure which runs parallel to the loop of Henle. Cortical nephrons are not associated with vasa recta. The function of the vasa recta as well as differences in function of cortical and juxtamedullary nephrons will be described in greater detail later.
In what part of the kidney are all renal corpuscles located?
What is the fxn of branching of glomerular capillaries?
What kind of endothelium do the glomerular capillaries have and what is the purpose?
What is the flow of fluid in the renal corpuscle?
All renal corpuscles are located in the cortex of the kidney. Each corpuscle has two parts, the glomerular capillaries and a Bowman’s capsule. Together these two parts are sometimes referred to as a glomerulus, although the term glomerulus commonly refers exclusively to the ball-like tuft of glomerular capillaries (as the term is used in this course). The glomerulus is where filtration of the plasma occurs. Figure 1.5 (attached) shows a renal corpuscle. Extensive branching of the glomerular capillaries maximizes their surface area. The endothelium of the glomerular capillaries is fenestrated to promote filtration. Bowman’s capsule encompasses the glomerular capillaries and is the start of the nephron. Filtered fluid in Bowman’s capsule moves directly into the next part of the nephron, the proximal tubule.
List the barriers to filtration.
The filtration pathway from the lumen of the glomerular capillaries to the lumen of Bowman’s capsule (called the urinary or Bowman’s space) has 3 layers. These 3 layers are:
Filter Layer 1 : the capillary endothelial cells
Filter Layer 2 : the glomerular basement membrane
Filter Layer 3 : the podocytes
What size particles/solutes are able to filter through the endothelial barrier? What substances in the plasma does it prevent and allow filtration through?
The endothelial cells of the glomerular capillaries are fenestrated to promote filtration. These fenestrations (or holes) in the endothelium are very nicely illustrated in Figure 1.5 (inset). The endothelial fenestrations are small enough to prevent the filtration (i.e. passage) of any cells (like RBCs). But, they are sufficiently large (∼70 nm, or about 10 times the diameter of serum albumin) to allow most solutes in the plasma to pass. Indeed, they are large enough for most plasma proteins to pass.
Describe the role of the glomerular basement membrane (GBM) in filtration.
What role does GBM play in proteinuria?
The glomerular basement membrane (GBM) is an important barrier to the filtration of plasma proteins. Plasma proteins have a net negative charge. The GBM also has a net negative charge (due to the presence of proteoglycans and glycoproteins). Like charges repel each other and thus the GBM is a significant barrier for plasma proteins to cross. In fact, plasma proteins larger than ~3 nm (or 30 Å) in diameter are rarely filtered because of the charged GBM. Note that hemoglobin and serum albumin have diameters larger than this. Figure 1.7 shows what happens when the negative charge of the GBM is lost (as sometimes occurs in certain glomerular diseases). Loss of GBM negative charge results in filtration of relatively large plasma proteins. This produces proteinuria (increased concentrations of plasma proteins in urine). It is important to note that the GBM – despite its negative charge – has no measurable effect on the filtration of small negatively charged solutes such as Cl- (diameter ∼0.2 nm).
What are podocytes?
What sized particles do podocytes allow to filter?
Podocytes are visceral epithelial cells of Bowman’s capsule. These cells have “foot processes” that inter-digitate to form “slit-like holes” or “filtration slits”. These slits do not permit the filtration of molecules in plasma with dimensions greater than ~8 nm. Thus, they help exclude things from the filtrate. Until recently, it was thought that the GBM was by far the most important barrier to the filtration of plasma proteins. However, new evidence suggests that the filtration slits formed by podocytes also play a substantial role as a barrier to protein filtration.
What are the functions of mesangial cells?
Mesangial cells serve a “cleansing function” in the renal corpuscle. They can also contract/constrict (under autonomic control) changing how fluid moves in renal corpuscle (i.e. changing filtration rate)-changing number of glomerular capillaries available for filtration
How is hydrostatic pressure in glomerular capillaries controlled?
What is the change in glomeular pressure with constriction of the afferent arteriole? Efferent arteriole?
Hydrostatic pressure in glomerulus controlled by relative vasoconstriction of afferent & efferent arterioles.
Afferent arteriole vasoconstriction-decrease glomerular pressure-decrease GFR
Efferent arteriole vasoconstriction-increase glomerular pressure-increase GFR
What does the juxtaglomerular apparatus (JGA) consist of? Explain the feedback signaling that occurs in the JGA concerning an increase in blood pressure.
The juxtaglomerular apparatus (JGA) consists of the macula densa and secretory granular cells (secrete renin). The basic structure of the juxtaglomerular apparatus is shown in Figure 1.9. The nephron tubules come into close association with the afferent and efferent arterioles that supply its own glomerulus (site where the tubular fluid first formed). This represents a point where feedback signaling can occur. Indeed, tubular fluid composition in the renal tubule is sensed at the JGA and then the JGA generates a signal that regulates tubular fluid formation at the glomerulus. This is a form of autoregulation (described in more detail later). This feedback is often called tubuloglomerular feedback.
A general feedback loop associated with the juxtaglomerular apparatus is shown in Figure 1.10 (attached, also slide 16 of notes). Here, the system is challenged with an increase in arterial blood pressure. This will increase the hydrostatic pressure in the glomerular capillaries and thus increases GFR (i.e. the rate tubular fluid is formed). This increases tubular flow past the macula densa (a specialized section of the distal tubule) and this is sensed. The macula densa cells release an agent that causes vasoconstriction of the afferent arteriole. Afferent arteriolar vasoconstriction reduces hydrostatic pressure in the glomerular capillaries and this helps return GFR to more normal levels. Thus, this feedback loop helps maintain an essentially constant GFR. The major unknowns concerning tubuloglomerular feedback are the precise mechanism by which increased flow through the macula densa is sensed and the precise nature of the vasoconstrictor substance released (although several hypotheses have been advanced in both cases; ATP has been implicated as part of the vasoconstrictor pathway).
What are the 3 major processes of the nephron? (list and describe)
What is excretion? How is it calculated?
The basic operation of the nephron can be broken down into three major processes. These are:
- Filtration
- Reabsorption
- Secretion
Note that excretion is the elimination of whatever is left over after these processes are complete. Thus, excretion is not generally thought of as a basic renal process.
Excretion= F + S-R
A. Filtration: As already described, filtration is the almost nonselective bulk movement of plasma from the glomerular capillaries into Bowman’s capsule. Plasma, of course, is blood without cells. The plasma (fluid & solutes) that crosses from the glomerular capillaries into Bowman’s capsule (the start of the nephron) is called the filtrate. The filtration barrier (described earlier) allows water and small solutes to pass. It does not allow blood cells or plasma proteins to pass. Indeed, the filtrate is virtually free of proteins – i.e., large plasma proteins do not normally leave the glomerular capillaries.
B. Reabsorption: Reabsorption is the selective transport of things in the filtrate back into the plasma of the peritubular capillaries. The various transport mechanisms in the epithelial cells of the various tubular segments that mediate this selective reabsorption will be described in later lectures. Water as well as many solutes are reabsorbed.
C. Secretion: Secretion is the selective addition of various solutes from the plasma of the peritubular capillaries (i.e. solutes that were not filtered) into the lumen of the nephron tubules. Secretion is generally the converse of reabsorption. As with reabsorption, secretion is selective due to the specificity of the transport mechanisms in the epithelial cells of the nephron tubules.
