Renal Physiology I Flashcards by Joel Glotfelty

Total body water is distributed between intracellular and extracellular compartments. The majority of total body water exists as

Intracellular fluid

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Shifts between intra- and extracellular water occur as directed by

Volume, electrolyte, and protein status

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Defined as the concentration of solutes in a given weight of H2O

Osmolality

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In the context of physiology, the osmotic state of the extracellular fluid is defined by

Iso- hypo- and hyperosmolality

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In the context of body fluid balance, total osmolality is not always important. Instead, we use the

Effective osmolality

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Effective osmolality is created by

Effective solutes

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Solutes which can not passively diffuse across cell membranes

-Example: Na+

Effective solutes

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Sets tonicity, that is the relative concentration that determines the direction and extent of H2O diffusion

Na+

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Cell membranes are permeable to ineffective solutes such as

Urea

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Not used to calculate effective osmolality, but IS used to calculate total osmolality

Urea (measured as Blood Urea Nitrogen; BUN)

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An effective solute since it is metabolized within cells and thus does not accumulate within cells

Glucose

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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

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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

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In this case, plasma volume will be

Reduced (ECF volume increases)

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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)

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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

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What 5 things do the Kidneys regulate?

) Plasma volume
) Blood pressure (BP)
) Waste excretion
) Electrolyte balance
) Plasma pH

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This regulation is accomplished by a system of structures known as

Nephrons

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A network of tubules, ducts, and microvasculature

Nephrons

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How many nephrons does each kidney contain?

Appproximately 1 x 10^6

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Each kidney is supplied with oxygenated, nutrient-rich blood by the

Renal artery

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Renal circulation receives approximately what percentafe of cardiac output?

20%

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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

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Characterized by a relatively high pressure and high compliment of vascular smooth muscle. This it is capable of high resistance

Afferent arteriole

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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?

1. ) Filtration 2. ) Reabsorption 3. ) 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 1. ) Young men 2. ) Young women

1. ) 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 1. ) Men 2. ) Women

1. ) 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?

1. ) Systemic BP 2. ) Blood flow within afferent arteriole 3. ) Glomerulr P which dictates GFR 4. ) 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

Renal Physiology I Flashcards

(100 cards)