Renal Physiology I Flashcards
Total body water is distributed between intracellular and extracellular compartments. The majority of total body water exists as
Intracellular fluid
Shifts between intra- and extracellular water occur as directed by
Volume, electrolyte, and protein status
Defined as the concentration of solutes in a given weight of H2O
Osmolality
In the context of physiology, the osmotic state of the extracellular fluid is defined by
Iso- hypo- and hyperosmolality
In the context of body fluid balance, total osmolality is not always important. Instead, we use the
Effective osmolality
Effective osmolality is created by
Effective solutes
Solutes which can not passively diffuse across cell membranes
-Example: Na+
Effective solutes
Sets tonicity, that is the relative concentration that determines the direction and extent of H2O diffusion
Na+
Cell membranes are permeable to ineffective solutes such as
Urea
Not used to calculate effective osmolality, but IS used to calculate total osmolality
Urea (measured as Blood Urea Nitrogen; BUN)
An effective solute since it is metabolized within cells and thus does not accumulate within cells
Glucose
What is the main difference between an effective and ineffective solute?
An effective solute creates an osmotic gradient, where as an ineffective solute does not
What happens if the ECF becomes hyperosmotic due to an increase in effective solute (i.e. Na+) concentration
Free H2O will move from plasma down its concentration gradient into the ECF
In this case, plasma volume will be
Reduced (ECF volume increases)
The blood volume that is required for adequate perfusion of the vital organs
- another way to describe stressed volume
- Not a static quantity that can be measured
Effective Circulating Volume (ECV)
The renal system senses changes in body fluid balance via changes in renal blood pressure and attempts to compensate by either
Conserving or eliminating Na+ and free H2O
What 5 things do the Kidneys regulate?
- ) Plasma volume
- ) Blood pressure (BP)
- ) Waste excretion
- ) Electrolyte balance
- ) Plasma pH
This regulation is accomplished by a system of structures known as
Nephrons
A network of tubules, ducts, and microvasculature
Nephrons
How many nephrons does each kidney contain?
Appproximately 1 x 10^6
Each kidney is supplied with oxygenated, nutrient-rich blood by the
Renal artery
Renal circulation receives approximately what percentafe of cardiac output?
20%
Within the kidney, the constituents of blood plasma are filtered as a result of the interactions between the
Afferent arteriole, glomerulus, efferent arteriole, and peritubular capillaries
Characterized by a relatively high pressure and high compliment of vascular smooth muscle. This it is capable of high resistance
Afferent arteriole
Has a large surface area and is loaded with fenestrations that allow filtration
Glomerulus
The efferent arterioles and paritubular capillaries are characterized by
Low pressure and flow
Mediated by 1) internal mechanisms, 2) the extra- and intrarenal endocrine systems (e.g., aldosterone, arginine vasopressin, angiotensin, and atrial natriuretic peptide), and 3) the autonomic nervous system
Renal function
The kidneys are innervated EXCLUSIVELY by the
SNS (NO PNS innervation)
Controls vasoconstriction of the renal microcirculation, Na+ reabsorption, and it stimulates secretion of renin
SNS activity
Which three processes in essence define renal function?
- ) Filtration
- ) Reabsorption
- ) Secretion
The movement of plasma constituents (i.e. H2O, ions, glucose, urea, and small proteins) from the glomerulus into Bowman’s capsule
Filtration
The movement of constituents from the tubule lumenal fluid (i.e. forming urine) into the renal intersitium, and/or recycling of these substances back into circulation
Reabsorption
The movement of constituents from renal circulation, interstitium, and/or tubule epithelium into the forming urine
Secretion
The adult kidneys filter about 120L of plasma/day. Assuming normal flid input of about 2L per day, the average urine output is approximately
0.8-2.0L per day
Therefore, it should be apparent that the default mode of renal function is the process of
Antidiuresis (reabsorption)
Blood enters the nephron via the
Afferent arteriole
Filtration (due to starling forces) occurs within the
-Filters approximately 180 L per day
Glomerulus
However, typically only about 1-1.5L of urine are excreted per day. Thus the vast majority of the glomerular filtrate is
Reabsorbed by the nephrons
Upon filtration, the filtrate flows from the collecting reservoir known as the Bowman’s Capsule throughout the
Renal tubule network
Within the tubule system, the forming urine is concentrated by the diffusion and/or transport of
H2O, ions, and urea
The osmolality of urine is dictated by plasma volume, which in turn depends upon the
Interstitial (ECF) osmolality
Urine osmolality is ultimately orchestrated by hormonal mechanisms that modulate H2O and Na+ reabsorption within the
Nephron and collecting duct
The early stages of renal disease are silent and can only be detected by lab analysis measuring the
Glomerular filtration rate (GFR) uring blood creatine and/or creatine clearance measurements
Hypertension, anemia, malnutrition, bone disease, neuropathy, and renal failure are some complications that stem from
Impaired renal function
Defined as the volume of blood that can be 100% cleared of a solute per unit time
-units are mL/min
Renal Clearance (C)
The rate at which filtrate is filtered from the glomerulus into Bowman’s capsule
Glomerular Filtration Rate (GFR)
The standard marker for determining renal function
GFR
Any changes in intrarenal BP that influence flow (renal perfusion) and/or the biochemical characteristics and/or ultrastructure of the glomerulus will affect
GFR
In a very general sense, as glomerular BP increases, what happens to GFR?
It will rise accordingly (and decrease in renal BP = decreased GFR)
In general, ions, glucose, H2O, and very small proteins can traverse the glomerular fenestrations fairly
Easily
What three things affect how readily substances can be filtered from the glomerulus?
MW, radius, and charge
Why do cations tend to cross the glomerular filtration barrier with less resistance than anions?
Because the glomerular filtration barrier has a negative charge
More complicated than GFR because it can be influenced by filtration, reabsorption, and secretion
Renal Clearance (C)
Clearance can be summarized into the following relationship
Arterial input = venous output + urine output
A direct measurement of renal function and is hence the best index of renal function
GFR
GFR is in fact the product of
Single nephron GFR x N (where N = total number of nephrons)
Interestingly, during the earliest phases of some kidney diseases (i.e. diabetic kidney disease), a compensatory increase in single nephron GFR (hyperfiltration) can mask a loss in
Nephron number
Will decrease prior to the onset of symptoms of renal disease
GFR
GFR decreases in direct correlation with the pathologic severity of
Kidney disease
These include kidney disease, pregnancy, reduced kidney perfusion, marked changes in extracellular fluid volume, non-steroidal anti-inflammatory drug (NSAID) use, acute/habitual elevated protein ingestion, blood glucose, and arterial BP
Pathophysiologic factors that will affect GFR
Glomerular function is measured using clearance as an indicator of
GFR
The process of renal autoregulation assists to control
GFR
Self governing glomerular regulation of intraglomerular pressure
Renal autoregulation
In general, increased systemic BP induces a myogenic response within the
Afferent arterioles
The resultant vasoconstriction of the afferent arterioles prevents potentially damaging increases in
Glomerular pressure (thus sustaining GFR)
On the other hand, very low BP is sensed within the
kidney, and in response, hormonal mechanisms are mobilized to induce vasoconstriction within the
Efferent arterioles
What is the normal GFR for
- ) Young men
- ) Young women
- ) GFR ≈ 130 ml/min/1.73 m^2
2. ) GFR ≈ 120 ml/min/1.73 m^2
After age 35, GFR generally decreases by about
1mL per year of age
Associated with a HIGH risk for the development of cardiovascular disease
GFR less than 60
At GFR less than 60, mortality from CV disease actually exceeds the risk of progression to
Renal failure
Indicates renal failure and would require replacement via dialysis or kidney transplant
GFR less than 15 mL/min/1.73 m^2
In order for GFR to be measured without very invasive approaches, GFR must equal
Clearance (C)
A fructose polymer that meets the criteria for measuring GFR where by GFR = C
Insulin
Isulin is not routinely used anymore because it is not cost effective and it is not endogenous so it must be injected to be measured. However, for all intents and purposes we can say that
C(insulin) = GFR
In clinical reality, we measure GFR by measuring
Creatinine
A metabolic by product of the muscle creatine phosphate reaction
Creatinine (Cr)
Measured in drawn blood
Serum creatinine (SCr or PCr for plasma creatinine)
SCr will vary between men and women with a greater value seen in
Men
Greater muscle mass will increase
PCr
Thus, assuming stready state conditions, basal SCr will generally fall within a standard range of
0.4-1.5 mg/dL
How much creatinine is excreted per day in
- ) Men
- ) Women
- ) 20-25 mg per day
2. ) 15-20 mg per day
The following relationships will exist in a healthy patient:
1.) Increased GFR will induce a decrease in
SCr
The following relationships will exist in a healthy patient:
2.) Decreased GFR will cause
Increased SCr and Blood Urea Nitrogen (BUN)
Blood Urea Nitrogen (BUN) is a product of
Protein metabolism
Although plasma creatinine levels remain relatively constant, BUN levels can fluctuate dramatically with changes in
Diet (high protein), metabolism, and importantly volume status
Make note that a high protein diet and volume depletion will each raise BUN, with the latter due to the increased renal tubule reabsorption of urea that accompanies
Na+ and H2O reabsorption
Thus, an elevation in BUN without an accompanying rise in creatinine is not a reliable indicator of
GFR
Two of the many equations that are used for the estimation of GFR based upon the relationship between SCr and CCr are the
CDK-Epi and Modification of Diet in Renal Disease (MDRD) equations
Can also be determined via the “24 hour urine”, a method that relies upon the total urine collection by the patient in a 24 hour period
Creatinine clearance (GFR)
All currently used methods used to estimate GFR have limitations. Thus screening for kidney disease requires the use of
Multiple markers of renal function
The amount of solute filtered into Bowman’s capsule per unit time
Filtered load
The ratio of solute excreted to that of the filtered load (in other words, how much of what gets filtered actually ends up in excreted urine)
Fractional Excretion (FE)
What are the forces within the afferent arteriole and the glomerular capillary that favor ultrafiltration?
Pcap and π-Bowman’s
I.e capillary hydrostatic pressure and Bowman’s colloid osmotic pressure
Within the afferent arteriole, and especially the glomerular capillary, the hydraulic forces (Pcap + π-Bowman’s) that favor ultrafiltration win-out; hence
Filtration occurs
As plasma enters the efferent arteriole, the opposing
forces (PBowman’s + πcap) increase concomitant with a decrease in the hydraulic forces; these forces oppose
Ultrafiltration
Which 4 things regulate input to the nepbhron?
- ) Systemic BP
- ) Blood flow within afferent arteriole
- ) Glomerulr P which dictates GFR
- ) Vasomotion within afferent and efferent arterioles
The key here is at the level of the
Afferent Arteriole
The greatest pressure drop in the renal system occurs between the
Afferent arteriole and glomerulus
-essentially no pressure drop occurs between afferent and efferent ends of glomerulus
This means that vasoconstriction and vasodilation of the afferent arteriole has a major impact on
Renal perfusion and GFR
In a simple model loss of blood pressure in the afferent arteriole means
Decreased GFR
