Flashcards in Basic Physiology, NORMAL LABS Deck (66):
What does the autoregulation response respond to and what is it?
• 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
What does the Hypovolemic response respond to and what is it?
• 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
What role in the response to hypovolemia do renal prostaglandins play?
• 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
What are the two different sensors of decreased Mean Arterial Pressure in the Kidney?
• Stimulation of arterial baroreceptor reflex
• Juxtaglomerular barorecptor stimulation
Where are the baroreceptors that first sense a decline in MAP?
• 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
What does the external baroreceptor reflex cause?
• Hormonally mediated constriction of the arterioles
• Through renin secretion and RAAS activation
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?
• 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
What is the range of autoregulation for RPF, Pgc and GFR?
• 75-150 mmHg
• This is why malignant hypertension is so hard on the kidneys
The afferent arteriole will maintain Pgc consistely by what mechanism?
• 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
What is Pgc and what is it compared to major arteries?
• 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
Does the body regulate ECF primarily by changing GFR?
• 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
What determines the opposing forces to filtration at Bowman's capsule?
• 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
What is K in the GFR equation?
• 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
What is the normal value of NFP?
• Net filtration pressure
• P-gc = 46mm
• P-t = 10mm
• Pi-gc (oncotic pressure) = 30mm
• NFP = 6mm
How can Ohms law be extrapolated to GFR?
• 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
What are the three barriers to filtration in the glomerular apparatus?
○ 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
○ Interdigitating epithelial cell membranes and membrane slits that act as molecular sieves
What is the molecular size cutoff for filterability in the glomerulus?
• Everything smaller then that has measured filterability, with the super small stuff being fully filterable
Where does filltration take place in the tubule?
• 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
What are the cells that secrete renin?
• Granular cells, specialized smooth muscle cells of the afferent arteriole
• Part of the juxtaglomerular apparatus
What should be considered the normal level of HCO3?
• Low twenties mEq/L
What should be considered the normal BUN in the blood?
• 7-18 mg/dL
Which should be considered the normal sodium level in the blood?
• 140 mEq/L
What should be considered the normal protein level total in the blood?
• 6-8 gm/dL
What should be considered the normal potassium level of the blood?
• Around four mEq/L
What should be considered the normal osmolality of the blood?
• Close to 290 mOsm/kg
What should be considered the normal level of creatinine in the blood?
• Just about one mEq/L
What should be considered the normal level of chloride in the blood?
• Low 100s mEq/L
Decreased blood pressure is sensed by the renal baroreceptor reflex and what is the result?
• 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
How much of the cardiac output is received by the kidneys?
• 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)
How do the kidneys affect the ECF?
• Indirectly. They influence the stationary interstitial fluid composition and volume by acting on its circulatory component, the plasma.
Describe the roadmap of renal physiology
• 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
Sodium and water are handled in the kidney according to what overall process?
• 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
What are the three processed performed by the nephron?
• 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
What is the basic unit of renal function?
• 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
What general ECF characteristics are regulated by the kidney?
• Electrolyte composition
• Metabolic wastes foreign substances
Renal corpuscles and renal tubules accomplish the two functions of the kidney. What are these functions?
• 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
Where is the mesangium?
• 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
What must filtrate go through to get to bowman's space?
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
where in the kidney are the renal corpuscles found?
The renal corpuscles are always found in the renal cortex.
After leaving the renal corpuscle, the filtrate passes through the renal tubule in what order?
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.
How quickly must urine specimens be tested for urinalysis?
• Within two hours of collection or they must be refrigerated
• 24 hour specimens cannot be used for urinalysis
What must be done if you are culturing urine for suspected UTI?
• Midstream clean catch
• Again, must be 2 hours or refrigerated
• Genitalia must be washed and rinsed then collected midstream
What is desireable about 24 hour urine collection?
• 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
What are the different possible results of the visual inspection of urinalysis in terms of volume?
• Over 24 hour collection period
§ More than 2L
§ Defective hormonal regulation of volume homeostasis
§ Defective renal salt/water absorption
§ Osmotic diuresis (DM)
§ Less than 500mL but more than 100mL
§ Ask: pre-renal? Postrenal? Renal parenchymal disease?
§ Less than 100mL
What do the different color results of urinaylsis visual inspection suggest?
○ Bile pigments (bilirubin)
○ Excreted urobilinogen
○ Hematuria, hemoglobinuria, myoglobinuria, porphyrias, beet ingestion
• Dark brown-black
○ Methemoglobin, rhabdomyolysis (cola colored), L-dopa, homogentisic acid (alkaptonuria)
What is up with the specific gravity test in urinalysis?
• 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
What might cause increased specific gravity?
• Addison's disease
What might cause decreased specific gravity?
• Diuretic therapy
• Diabetes insipidus (not DM)
What does it mean to check osmolality by urinalysis?
• 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
In what situations is the specific gravity measurement especially helpful?
• 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
What does acidic urine indicate?
• pH of urine usually reflects pH of serum
• Metabolic or respiratory acidosis, drugs, diet high in protein, cranberries
What does alkaline urine indicate?
• 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)
What is normal protein in the urine?
• Less than 0.5g/day
What are the caveats with protein detection by dispstick we should know about?
• 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
What level of hyperglycemia would result in glucosuria?
• Over 180-200 mg/dL and the kidney can't resorb all the glucose and some will show up in the urine
What conditions might show ketouria because of increased lipid metabolism?
• Diabetes, alcoholism, cirrhosis, prolonged fast, heavy exercise
What's up with hemosiderin on the dipstick?
• 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
What does looking for leukocyte esterase do?
• 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
If you get positive neutrophil numbers in UA, where else could it come from?
• Vaginal secretions, glomerulonephritis, tochomonads and eosinophils (worm infection)
What are the insoluble materials that necessitate centrifugation of the urine to see?
• Organisms (bacteria)
If you see waxy casts on microscopic UA, what are you worried about?
• Waxy casts, sharp margins, blunt ends, cracks in lateral margins, 8-12 RBCs wide
• ASSOCIATED WITH ADVANCED CHRONIC RENAL FAILURE
What does stimulation of arterial baroreceptor reflex do?
• 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
What is considered normal plasma CPK?
10 to 120 micrograms per liter (mcg/L)
What is considered normal plasma calcium?
Adult = 8.6-10.2 mg/dL
What is considered normal plasma phosphate?
Adults = 2.5 to 4.5 mg/dL.