Basic Physiology, NORMAL LABS

Question 1

What does the autoregulation response respond to and what is it?

Answer 1

• Rapid, normal fluctuations up or down in MAP within normal range
  
  • The purpose is to maintain GFR, RBF constant under normal conditions
  • The afferent arterioles are involved and are involved by a myogenic mechanism
  • This mechanism is intrinsic to the kidney

Question 2

What does the Hypovolemic response respond to and what is it?

Answer 2

• Responds to Chronic, significant drops in MAP below normal range due to hypovolemic events
  
  • The purpose is to maintain GFR pretty much constant (small decrease) but reduce RBF during circulatory emergencies
  • The afferent AND efferent arterioles are involved in this response
  • Arterioles are regulated by baroreceptor reflex AND by direct sympathetic innervation AND by hormal action
  • This reflex is both intrinsic to the kidney and it has extrinsic input as well

Question 3

What role in the response to hypovolemia do renal prostaglandins play?

Answer 3

• Produced by renal interstitial cells in the kidney medulla
  
  • They have a local dilatory effect on renal arterioles
  • Secreted in response to angiotensin II presence
  • The point is to maintain a decent renal blood flow to the tissue itself even if there is hypovolemia
  • The tubular cells are super whiny to hypoxia

Question 4

What are the two different sensors of decreased Mean Arterial Pressure in the Kidney?

Answer 4

• Stimulation of arterial baroreceptor reflex

* Juxtaglomerular barorecptor stimulation

Question 5

Where are the baroreceptors that first sense a decline in MAP?

Answer 5

• Baroreceptors in the main arteries
  
  • If the decrese is significant and long lasting, a baroreceptor reflex occurs in which the activity of the renal sympathetic nerve increases
  • Sympathetic nerve action increases the constriction of both the efferent and the afferent arterioles which allows the GFR to be held pretty constant considering the change in pressure

Question 6

What does the external baroreceptor reflex cause?

Answer 6

• Hormonally mediated constriction of the arterioles

* Through renin secretion and RAAS activation

Question 7

The kidney doesn’t want to shut off completely even when it’s trying to shunt blood volume to the heart (response to hypovolemia). How does it compensate?

Answer 7

• There is both afferent and efferent arteriole constriction
  
  • The afferent arteriole constriction will shunt blood away from the kidneys
  • The efferent arteriole constriction will allow what blood does go through the proper forces to maintain GFR

Question 8

What is the range of autoregulation for RPF, Pgc and GFR?

Answer 8

• 75-150 mmHg

* This is why malignant hypertension is so hard on the kidneys

Question 9

The afferent arteriole will maintain Pgc consistely by what mechanism?

Answer 9

• Myogenic mechanism
  
  • The smooth muscle in the afferent arteriole recognizes changes in pressure and constricts or dilates accordingly
  • This can be overwhelmed but a healthy person operates within the range of accomodation

Question 10

What is Pgc and what is it compared to major arteries?

Answer 10

• Pgc is the hydrostatic pressure in the blood vessels at bowmann’s capsule. This is the driving force for filtration in the glomerulus
  
  • It is about 1/2 of MAP in major systemic arteries
  • It really must be maintained at a constant level to allow for GFR to remain constant. The opposing forces to filtration don’t change so the pressure must be tightly regulated

Question 11

Does the body regulate ECF primarily by changing GFR?

Answer 11

• No, the body works pretty hard to maintain GFR constant

* It changes the amount or specificity of reabsorption to control the ECF by controlling what is in the plasma

Question 12

What determines the opposing forces to filtration at Bowman’s capsule?

Answer 12

• Hydrostatic pressure is the only force towards filtration in the capsule and that is controlled by blood pressure in the capillaries that pass by the capsule
• Backflow from the natural resistance of the filtration layers of the capsule provide a small anti-filtration force
• The largest anti-filtration force is the oncotic pressure that is exerted by large proteins albumin and immunoblobulins in the plasma that are not freely filterable
○ COP or colloid osmotic pressure
• Thus GFR= K(hydrostatic pressure - transmural pressure - oncotic pressure)
• The sum of forces is called the NFP OR NET FILTRATION PRESSURE

Question 13

What is K in the GFR equation?

Answer 13

• GFR = K(NFP)
  
  • K represents the total hydraulic conductivity of the kidneys
  • How much fluid will flow across the glomerulus per unit of time for each unit of pressure
  • Made up of p*A
  • P is the specific hydraulic conductivity
  • A is the surface area of all the glomeruli - the main contributor in the largeness of K

Question 14

What is the normal value of NFP?

Answer 14

• Net filtration pressure
  
  • P-gc = 46mm
  • P-t = 10mm
  • Pi-gc (oncotic pressure) = 30mm
  • NFP = 6mm

Question 15

How can Ohms law be extrapolated to GFR?

Answer 15

• GFR = change in pressure/resistance
  
  • The pressure difference is across the filtration layers and R is the resistance of those layers to flow which doesn’t normally change so is given a constant value

Question 16

What are the three barriers to filtration in the glomerular apparatus?

Answer 16

• Endothelium
○ Through the fenestrations
○ Pretty much only exclude circulating RBCs
• Basal lamina
○ Created and supported by the podocytes and the endothelial cells
○ Composed of mucoproteins
○ Essentially an agarose gel that filters stuff by size
• Podocytes
○ Interdigitating epithelial cell membranes and membrane slits that act as molecular sieves

Question 17

What is the molecular size cutoff for filterability in the glomerulus?

Answer 17

60kDa

• Everything smaller then that has measured filterability, with the super small stuff being fully filterable

Question 18

Where does filltration take place in the tubule?

Answer 18

• Across the capillary loops into Bowman’s capsule of the tubule
  
  • The arterioles are the structures that regulate blood and plasma flow through the glomerulus

Question 19

What are the cells that secrete renin?

Answer 19

• Granular cells, specialized smooth muscle cells of the afferent arteriole
  
  • Part of the juxtaglomerular apparatus

Question 20

What should be considered the normal level of HCO3?

Answer 20

• Low twenties mEq/L

Question 21

What should be considered the normal BUN in the blood?

Answer 21

• 7-18 mg/dL

Question 22

Which should be considered the normal sodium level in the blood?

Answer 22

• 140 mEq/L

Question 23

What should be considered the normal protein level total in the blood?

Answer 23

• 6-8 gm/dL

Question 24

What should be considered the normal potassium level of the blood?

Answer 24

• Around four mEq/L

Question 25

What should be considered the normal osmolality of the blood?

Answer 25

• Close to 290 mOsm/kg

Question 26

What should be considered the normal level of creatinine in the blood?

Answer 26

• Just about one mEq/L

Question 27

What should be considered the normal level of chloride in the blood?

Answer 27

• Low 100s mEq/L

Question 28

Decreased blood pressure is sensed by the renal baroreceptor reflex and what is the result?

Answer 28

* Release of Renin * Renin cleaves angiotensinogen to angiotensin 1 * Angiotensin 1 is cleaved into angiotensin 2 by ACE (lungs) * Angtiotensin 2 is a potent vasoconstrictor that increases blood pressure

Question 29

How much of the cardiac output is received by the kidneys?

Answer 29

* 25%. More than any other organ system besides lungs * 5L/min cardiac output means 1.3L /min goes through kidney * Hemocrit of 50% means 650mL/min through the kidney of plasma * 20% of this is filtered in glomerular filtration (filtration fraction of 0.2)

Question 30

How do the kidneys affect the ECF?

Answer 30

• Indirectly. They influence the stationary interstitial fluid composition and volume by acting on its circulatory component, the plasma.

Question 31

Describe the roadmap of renal physiology

Answer 31

* The plasma is the start of the roadmap, and the plasma is considered the mobile part of the interstitial fluid. If the plasma can be moved, the body's ECF can be regulated and renewed * The plasma (serrogate for interstitial fluid) undergoes FIRST filtration * SECOND is tubular processing * THIRD is the ECF sensors that regulate tubular processing * FOURTH is excretion * Finally, remember that reabsorption and secretion get things back into the plasma

Question 32

Sodium and water are handled in the kidney according to what overall process?

Answer 32

* Tubular secretion * Epithelial transport process that involves the movement of substances from the blood or blood side of the tubule into the tubular lumen * Often involves specific energy dependent transports

Question 33

What are the three processed performed by the nephron?

Answer 33

• Glomerular filtration ○ Filters plasma into the initial part of the tubule ○ Water and solutes into tubule, retains larger colloids like proteins, lipid aggregates and circulating blood cells • Tubular reabsorption ○ Recapture filtered components the body needs ○ Transport across epithelia cell layer with selective transporters ○ Rate of individual compenents reabsorption can be regulated • excretion

Question 34

What is the basic unit of renal function?

Answer 34

* The nephron * 1 million nephrons per functional kidney * Consists of blood supply and an epithelial tube (tubule) * Blood supply is two capillary beds in series, glomerular and peritubular

Question 35

What general ECF characteristics are regulated by the kidney?

Answer 35

* Volume * Osmolarity * Electrolyte composition * pH * Metabolic wastes foreign substances

Question 36

Renal corpuscles and renal tubules accomplish the two functions of the kidney. What are these functions?

Answer 36

• Corpuscles - filtration • Tubules - selective reabsorption How far into the medulla do nephrons go? • Juxtamedullary nephrons go the deepest and cortical nephrons extend to different depths but not as deep as the juxtaglomerular nephrons go

Question 37

Where is the mesangium?

Answer 37

* Made up of mesangial cells Within the more central regions of the glomerulus * They support the glomerular structure * They help to secrete part of the basal lamina * They are phagocytic and are thought to play a role in maintenance of the filtration lamina in the inner portion of the glomeruli

Question 38

What must filtrate go through to get to bowman's space?

Answer 38

1. pass through the fenestrated capillary epithelium (fenestrations are 50-100nm in diameter) 2. pass through the thick basement membrane (main filtration barrier) 3. pass though filtration slits between the podocyte feet

Question 39

where in the kidney are the renal corpuscles found?

Answer 39

The renal corpuscles are always found in the renal cortex.

Question 40

After leaving the renal corpuscle, the filtrate passes through the renal tubule in what order?

Answer 40

1) proximal convoluted tubule (found in the renal cortex) 2) loop of Henle (mostly in the medulla) 3) distal convoluted tubule (found in the renal cortex) 4) collecting tubule (in the medulla) 5) collecting duct (in the medulla) * The beginning of the distal convoluted tubule is found close to the renal corpuscle, in a structure known as the juxtaglomerular complex.

Question 41

How quickly must urine specimens be tested for urinalysis?

Answer 41

* Within two hours of collection or they must be refrigerated * 24 hour specimens cannot be used for urinalysis

Question 42

What must be done if you are culturing urine for suspected UTI?

Answer 42

* Midstream clean catch * Again, must be 2 hours or refrigerated * Genitalia must be washed and rinsed then collected midstream

Question 43

What is desireable about 24 hour urine collection?

Answer 43

* Urine protein electrophoresis can be done * Urine electrolytes can be measured * Total protein can be measured * Hormones can be measured * You are getting an AVERAGED data set, not just a tiny snapshot

Question 44

What are the different possible results of the visual inspection of urinalysis in terms of volume?

Answer 44

• Over 24 hour collection period ○ Polyuria § More than 2L § Defective hormonal regulation of volume homeostasis § Defective renal salt/water absorption § Osmotic diuresis (DM) ○ Oliguria § Less than 500mL but more than 100mL § Ask: pre-renal? Postrenal? Renal parenchymal disease? ○ Anuria § Less than 100mL

Question 45

What do the different color results of urinaylsis visual inspection suggest?

Answer 45

``` • Yellow-green-brown ○ Bile pigments (bilirubin) • Orange-red-brown ○ Excreted urobilinogen • Pink-red ○ Hematuria, hemoglobinuria, myoglobinuria, porphyrias, beet ingestion • Dark brown-black ○ Methemoglobin, rhabdomyolysis (cola colored), L-dopa, homogentisic acid (alkaptonuria) ```

Question 46

What is up with the specific gravity test in urinalysis?

Answer 46

• Indicates kidney's concentrating ability • Reflects relative proportion of dissolved solid components to total volume of the specimen • Can be decreased or increased ○ Less than 1.001 is decreased ○ More than 1.035 is increased

Question 47

What might cause increased specific gravity?

Answer 47

* Dehydration * DM * Proteinuria * CHF * Addison's disease * SIADH

Question 48

What might cause decreased specific gravity?

Answer 48

* Polydipsia * Diuretic therapy * Diabetes insipidus (not DM)

Question 49

What does it mean to check osmolality by urinalysis?

Answer 49

* Osmolality = number of particles of solute per volume of solution * Normal = 500-850 mOsm/kg water * Usually increases as specific gravity increases unless the solute is abnormal = glucose, protein

Question 50

In what situations is the specific gravity measurement especially helpful?

Answer 50

• Situations of acute oliguria ○ High specific gravity (over 1.01) suggests intact tubular function and pre-renal source of oliguria ○ Fixed isosthenuria (1.008-1.012) suggests renal tubular dysfunction, likely renal tubular acidosis • Interpreting other subtle abnormalities ○ Slight levels of protein or cells may be discounted in the setting of high specific gravity

Question 51

What does acidic urine indicate?

Answer 51

* pH of urine usually reflects pH of serum | * Metabolic or respiratory acidosis, drugs, diet high in protein, cranberries

Question 52

What does alkaline urine indicate?

Answer 52

* pH of urine usually reflects pH of serum * Renal tubular acidosis (hallmark), UTIs, excess bicarb ingestion, respiratory or metabolic alkalosis, several foods like citrus or just a large meal * If UTI, really alkaline urine suggests urea splitting organism (proteus or staghorn calculi)

Question 53

What is normal protein in the urine?

Answer 53

• Less than 0.5g/day

Question 54

What are the caveats with protein detection by dispstick we should know about?

Answer 54

* Sensitive to albumin only * Bence-jones protein (antibody part that is indicative of multiple myeloma), easy to miss on dipstick, need to use electrophoresis and immunofixation * Markedly alkaline urine may give falsely low results b/c pH dependent * Microalbuminuria also not detected by dipstick as it's below detectable range

Question 55

What level of hyperglycemia would result in glucosuria?

Answer 55

• Over 180-200 mg/dL and the kidney can't resorb all the glucose and some will show up in the urine

Question 56

What conditions might show ketouria because of increased lipid metabolism?

Answer 56

• Diabetes, alcoholism, cirrhosis, prolonged fast, heavy exercise

Question 57

What's up with hemosiderin on the dipstick?

Answer 57

* Renal tubules catabolize hgb to ferritin and hemosiderin and thus positive hemosiderin is a marker of 2-3 days post hemolytic episode * They show yellow-brown granules on Prussian Blue stain

Question 58

What does looking for leukocyte esterase do?

Answer 58

* Tests for urinary tract infection * Neutrophils make leukocyte esterase as part of the lysosomal hydrolyzing mechanisms to destroy engulfed bacteria * Esterase is an indirect measure of the number of neutrophils present in urine

Question 59

If you get positive neutrophil numbers in UA, where else could it come from?

Answer 59

• Vaginal secretions, glomerulonephritis, tochomonads and eosinophils (worm infection)

Question 60

What are the insoluble materials that necessitate centrifugation of the urine to see?

Answer 60

* Cells * Casts * Crystals * Organisms (bacteria)

Question 61

If you see waxy casts on microscopic UA, what are you worried about?

Answer 61

* Waxy casts, sharp margins, blunt ends, cracks in lateral margins, 8-12 RBCs wide * ASSOCIATED WITH ADVANCED CHRONIC RENAL FAILURE

Question 62

What does stimulation of arterial baroreceptor reflex do?

Answer 62

• Increases the firing rate of renal sympathetic nerve ○ This also leads to JGA renin secretion and RAAS activation • This leads to increased consriction of afferent and efferent arterioles ○ This decreases Renal Blood Flow • The Pgc is held constant • The end result is a modest to moderat DECREASE in GFR ○ The filtration force is reduced a bit and the oncotic force is actually increased

Question 63

What is considered normal plasma CPK?

Answer 63

10 to 120 micrograms per liter (mcg/L)

Question 64

What is considered normal plasma calcium?

Answer 64

Adult = 8.6-10.2 mg/dL

Question 65

What is considered normal plasma phosphate?

Answer 65

Adults = 2.5 to 4.5 mg/dL.

Question 66

What is "normal saline"?

Answer 66

0. 9% (NaCl) with an osmolarity of 308 mOsmol/L (calc). It contains 154 mEq/L sodium and 154 mEq/L chloride. * compare serum sodium to normal saline sodium and that should help you determine if it will help or hurt the overall sodium levels