Topic 1 - An Introduction to Renal Function

Question 1

Why do the kidneys produce urine?

Answer 1

the kidney’s filtration of blood, and modification of that filtrate by epithelial transport, produces urine in order to accomplish:

• excretion of metabolic waste products and foreign products
• regulatory control of body fluid volume, blood pressure, osmolality, electrolytes, and acidity

Question 2

What are the hormonal and biosynthetic functions of the kidney?

Answer 2

production and secretion of renin, erythropoietin, the activation of vitamin D, formation of arginine, and the performance of gluconeogenesis

Question 3

What are the endocrine functions of the kidney?

Answer 3

renin, erythropoietin, active form of vitamin D

Question 4

What are the synthetic functions of the kidney?

Answer 4

gluconeogenic (i.e. the synthesis of glucose from amino acids and other non-carbohydrate precursors; 2nd only to the liver in order of magnitude)

source of arginine biosynthesis

Question 5

What is erythropoietin?

Answer 5

a large glycoprotein hormone that is produced by the interstitial cells of the kidneys

acts on bone marrow to stimulate the conversion of hemopoietic stem cells to proerythroblasts

stimulated when oxygen levels in the blood are chronically low

• interstitial cells int he kidney located at the corticomedullary border, contain a heme-like proteint hat acts as an oxygen sensor
• hypoxic conditions, this sensor leads to an increase in a hypoxia inducible transcription factor (HIFF), which induced the erythropoietin gene to produce more hormone

Question 6

What is gluconeogenesis?

Answer 6

during a fast, the epithelial cells of the proximal tubule undergo that contributes a significant amount of glucose to the circulation

under hormonal control by glucagon, corticosteroids, epinephrine

also stimulated by metabolic acidosis (together with the production of alpha-KG and 2NH3 from glutamine)

• hexokinase is low in the proximal tubule and highest in the distal tubule where energy is derived from glycolysis
• glucose reabsorbed by the proximal tubule cells or made by gluconeogenesis does not undergo glycolysis, but rather is available from transport back to the circulation

Question 7

What is arginine?

Answer 7

normally the kidney is a major source

in renal disease, synthesis may wane, and arginie must be absorbed through the diet (thus becoming an essential amino acid)

Question 8

What is the active form of vitamin D?

Answer 8

the mitochondria of the proximal tubuel are the site of activation of 25-OH D3 to activate form 1,25-di-OH D3

Question 9

What is renin?

Answer 9

produced by the kidney and released into the vasculature as part of the renin, angiotensin, aldosterone system (RAAS)

• this system is so critical to clinical medicine

Question 10

What are some consequences of renal failure?

Answer 10

renal failure -> decrease 1,25-(OH)2 D3 -> decrease Ca2+ from GI -> decrease Ca2+ -> increase PTH -> decrease bone demineralization

decrease erythropoietin -> decrease Hct

increase renin-angiotensin -> increase arterial blood pressure

increase Na+ -> increase ECV -> increase arterial blood pressure

increases in:

• PO4
• BUN
• Creatinine
• uric acid
• organic anions and cations
• Na+
• K+
• H+

Question 11

How does age affect kidney function?

Answer 11

general decline of renal function after the age of 30yrs

renal function in a patient of 80yrs may be less than that 50% of what it was at 30yo

important when prescribing medications that are principally cleared by the kidney, to older patients

Question 12

What is compensatory hypertrophy?

Answer 12

removal or loss of a kidney is associated with compensatory hypertrophy of the contralateral kidney such that renal function will return to ~85% of the original value

this compensatory response is diminished with advancing age

Question 13

What are nephrons?

Answer 13

each nephron is a ‘little kidney’

function of kidney basically represents aggregated function of its nephrons

Question 14

What is the general house cleaning strategy of the kidney?

Answer 14

filter massive quantities of the plasma water and solutes into the renal tubules, then reabsorb those substances by tubular epithelial transport that are valuable and needed for the maintenance of homeostasis

• anything that is filtered and not subsequently reabsorbed is excreted in the urine
• selected solutes are secreted into the renal tubules by epithelial transport and excreted in the urine

Question 15

What is a simplified view of the nephron?

Answer 15

water and small solutes get filtered out of the plasma as the arterial blood flows through glomerular capillaries

this glomerular filture passes into the first part of the urinary tubule, which is called Bowman’s space

as glomerular filtrate passes on through the tubule

• most of the filtered fluid and most of the filtered solute is reabsorbed (and returned to the blood stream in the peritubular capillaries)
• some additional select solutes are secreted into the tubular fluid
• the fluid remaining in the tubule at the end becomes excreted in the urine

Question 16

What equation acounts for if water or any particular solute passes through the tubule?

Answer 16

excreted (mg/min) = filtered (mg/min) - reabsorption (mg/min) + secretion (mg/min)

E = F-R+S

Assumptions:

• x gets into the tubule by filtration and/or secretion: F + S
• x gets out of the tubule by reabsorption and/or excretion: R+E
• F+R = R+E -> E = F-R+S

apply to renal tubule?

• x is not destroyed (metabolized) in the tubular fluid
• x is not created (synthesized) in the tubular fluid
• x does not accumulate in the tubular fluid (i.e. tubular fluid does not ‘store up’ x and then suddenly ‘dump’ it at a later time)

Question 17

How are blood cells handled by the kidneys?

Answer 17

Filtered: no

Reabsorbed: no

Secreted: no

Excreted: no

Question 18

How are plasma proteins handled by the kidneys?

Answer 18

Filtered: no

Reabsorbed: no

Secreted: no

Excreted: no

Question 19

How are water handled by the kidneys?

Answer 19

Filtered: yes

Reabsorbed: yes

Secreted: no

Excreted: yes (some..1% of what is filtered)

Question 20

How are Na+ ions handled by the kidneys?

Answer 20

Filtered: yes

Reabsorbed: yes

Secreted: no

Excreted: yes (some..1% of what is filtered)

Question 21

How is glucose handled by the kidneys?

Answer 21

FIltered: yes

Reabsorbed: yes

Secreted: no

Excreted: no

Question 22

How is creatinine handled by the kidneys?

Answer 22

Filtered: yes

Reabsorbed: no

Secreted: no * (small amount)

Excreted: yes (all that is filtered)

Question 23

How is inulin handled by the kidneys?

Answer 23

Filtered: yes

Reabsorbed: no

Secreted: no

Excreted: yes (all that is filtered)

Question 24

How is PAH handled by the kidneys?

Answer 24

Filtered: yes

Reabsorbed: no

Secreted: yes

Excreted: yes (all that is in the renal plasma)

Question 25

All of the following substances are produced by the kidney EXCEPT:

a. renin
b. aldosterone
c. erythropoietin
d. vitamin d

Answer 25

b. aldosterone

Question 26

The most common cause of chornic kidney disease (CKD) in the United States is:

a. diabetes
b. hypertension
c. glomerulonephritis
d. polycystic kidney disease

Answer 26

a. diabetes

Question 27

Chronic kidney disease, sometimes referred to as uremia (aka azotemia), may cause which of the following conditions:

a. itching
b. edema (swelling) of the extremities
c. anemia
d. all of the above

Answer 27

d. all of the above

uremia is the term given to a constellation of symptoms, resulting from kidney failure with a resultant buildup of waste products in the circulation

some of the typical symptoms include: fatigue (often resulting from anemia), itching, dyspnea or edema from fluid retention, skin pallor or yellowish cast, foamy urine (due to protein), and nocturia

loss of protein in the urine >3.5g/d is referred to as nephrotic syndrome

Question 28

All of the following conditions are associated with chronic kidney disease EXCEPT:

a. low hemoglobin
b. hypoparathyroidism
c. hyperkalemia
d. hyperphosphatemia

Answer 28

b. hypoparathyroidism

numerous abnormalities of the blood, protein, and electrolytes occur in chronic kidney disease

• anemia is very common due to frequent blood loss with resulting iron deficiency and diminished secretion of erythropoietin by the diseased kidney
• calcium absorption is impaired due to inadequate calcitrol
• phosphate is not adequately excreted by the tubules, resultin in elevated phosphate producing so-called secondary hyperparathyroidism
  
  • may result in calcium deposition in the heart and blood levels
• elevated potassium levels are quite common and may be life-threatening

Question 29

Substance x is filtered by the kidney at a rate of 100mg/min. it is excreted in the urine at a rate of 20mg/min.

a. based on this information, how is this substance handled by the kidney?
b. what is the rate of tubular reabsorption?
c. what fraction of the filtered load of substance x is excreted?
d. what fraction of hte filtered load of substance x is reabsorbed?

Answer 29

a. we can assume it is filtered and reabsorbed, since the amount excreted is less than the amount filtered. if the excreted amount were greater than the amount filtered, we would conclude it is filtered and secreted; if it were the same amount filtered, we would conclude it was only filtered
b. Ex = Fx - Rx + Sx

20 = 100 - R + S(none)

R = 100-20 = 80 mg/min

c. fractional excretion substance x = Ex/Fx

FEx = 20/100 = 0.2

fractional excretion is usually expressed as a percentae rather than a fraction, so: 20%

d. fractional reabsorption of substance x = Rx/Fx

FRx = 80/100

FRx = 0.80 = 80%