Unit 4 - Renal Flashcards
Describe in a single sentence the role of the kidney in total body homeostasis
The main physiological function of the kidneys is the maintenance of the composition and volume of the ECF
State the volume of each of the major body compartments in a standard-sized, healthy, adult individual
- total body water = 42L
- ICF = 27L (noncirculating cell volume = 24L, RBCs = 3L)
- ## ECF = 15L (interstitial fluid = 12L, plasma = 3L)
Describe the major components and volumes of daily water intake and loss
- 2L ingested
- .5L metabolically produced
- 1L through sweat, feces, skin
- 1.5L through urine
Identify the processes of water intake and output that are regulated to achieve extracellular fluid homeostasis
- for most regulated substances, ingestion is in excess of incidental losses –> ECF constancy is achieved by regulating urinary output
- regulates volume, osmolarity, electrolytes, pH of ECF
Identify the basic functional structures of the nephron
- blood supply and epithelial tube
- blood supply is two capillary beds in series (glomerular and peritubular capillaries)
- afferent arteriole –> glomerular capillary –> efferent arteriole –> peritubular capillary
Describe the basic glomerular and tubular processes and how they interact to achieve ECF homeostasis
three processes
1) glomerular filtration
- filter plasma into initial part of tubule
- free passage of H2O and solutes into tubule
- bigger stuff like proteins, lipids, and RBCs stay in capillaries
2) tubular reabsorption
- transport filtered stuff that wants to regulate across epithelial cell layer using transporters
- regulate rate of reabsorption so that just enough ECF components are returned to plasma for ECF constancy
3) excretion
- substance in excess of required ECF balance amount pass through tubule through urine
4) secretion
- movement of substances from blood into tubular lumen
For a normal sized healthy individual, state the magnitude of renal blood flow, renal plasma flow, glomerular filtration rate, filtration fraction, and urine flow rate
- RBF = 1.3L/min
- RPF = .65L/min
- GFR = 130mL/min
- FF = .2
- UFR = 1.5L/day
Describe regulation of vascular resistance by angiotensin II via the baroreceptor-mediated renin-angiotensin axis
- regulate circulating levels of angiotensin
- dec BP –> sensed by baroreceptors to inc renin secretion –> converts angiotensinogen to AT1 –> AT1 goes to lungs –> ACE converts AT1 to AT2 –> causes arteriolar vasoconstriction and inc in MAP
- *level of renin is rate-limiting for the production of AT2 and thus determines the status of the axis
Why is it beneficial for the kidneys to recycle almost 99.9% of filtered stuff?
- kidneys are sentinels of ECF
- large capacity of GI system to add stuff to ECF in short time
- renal system removes excess ingested substances to prevent buildup in ECF
- basically in standby mode for a lot of the time, but can respond rapidly to excessive ingestion
- waste removal is not hugely important
- basically high filtration allows kidneys to quickly remove waste
- high filtration and reabs allows kidneys to precisely and rapidly control the volume and composition of body fluids
What are non-ECF functions of the renal system?
- produce EPO for RBC production –> renal failure can lead to anemia
- gluconeogenesis
What are normal values for bicarb, Cl, Cr, osm, K, protein, Na, and BUN (don’t need to memorize)
- bicarb 18-23 mEg/L
- Cl 98-106 mEq/L
- Cr .6-1.2 mg/dL
- osm 280-296 mOsm/kg
- K 3.5-5 mEq/L
- protein 6-8.4 gm/dL
- Na 135-145 mEq/L
- BUN 7-8 mg/dL
Describe the arteriolar, capillary, and epithelial components of the filtration apparatus
- filtration occurs across capillary loops into bowman’s capsule
- afferent and efferent arterioles control flow of plasma/blood and GFR
- granular cells (SMCs of afferent arteriole) secrete renin and are part of juxtoglomerular apparatus
Describe the ultrastructural basis for molecular sieving during glomerular filtration
- cut-off size for filtration is about 60kDa (albumin is slightly larger)
- three layers of filtration
1) endothelium - fenestrated epithelium; excludes RBCs; holes are fairly large
2) *basal lamina - thick BM secreted by endo and epi cells; mucoproteins which are large acidic sugars attached to protein cores; meshwork for filtration; negatively charged so ~60kDa pos charged filter better;
3) *podocytes - tubular epithelial cells; intertwined feet with slit membranes that connect feet; acts as a molecular sieve
Describe the Starling forces that drive and oppose glomerular filtration
- Pgc (hydrostatic pressure within glomerular capillary) drives fluid out; main driving force for filtration
- Pt is backflow from bowman’s capsule back into the glomerulus
- Pigc is flow into the glomerulus due to large dissolved proteins in the plasma like albumin
- Pit is fairly nonexistent since no large dissolved proteins there
State the Starling equation for glomerular filtration rate
GFR = K*(Pgc-Pt-pigc)
State the typical magnitude of each of the Starling forces and the resultant net filtration pressure
Pgc = 46mmHg Pt = 10mmHg pigc = 30mm NFP = 6mmHg out into bowman's capsule
- to get such a high GFR, K must be really high which is determined by conductivity and surface area
- surface area is about 1m^2
Define the process of autoregulation of GFR and RBF, including the structures involved, the cellular mechanisms, and physiological context and limitations under which this process operates
- filtration process is nonspecific –> keeps GFR constant and changes tubular reabs/secretion of regulated substances to “fine tune”
- changes in MAP do not cause proportional changes to glomerular capillary pressure
- Pgc is autoregulated
Structures involved:
- afferent areriole is regulating valve to keep renal blood flow constant
- Pgc and GFR also stay constant
Cellular mechanisms:
- myogenic: MAP changes smooth muscle cells of arteriole to constrict or dilate to keep downstream capillary blood flow constant
Physiological context:
- short term inc in MAP –> afferent arteriole constricts –> GFR and RBF are maintained
- opposite for short term dec in MAP
Limitations:
- good from MAP 75-150mmHg pressure range
- some residual error so upward creep of RBF and GFR and Pgc
- outside of range they change a lot
Define the process of hypovolemic regulation of GFR and RBF including the structures involved, the cellular mechanisms, and physiological context under which this process operates
- when sever vol dec, need to shunt blood to heart, brain, and lungs, so kidneys are underperfused, but want to keep some blood flow because important
- vasoconstricts afferent and efferent arterioles with severe dec in MAP
Structures involved:
- afferent and efferent arterioles constrict with severe hypotension
Cellular mechanisms:
- 1) normal baroreceptors sense dec in MAP –> renal sympathetic activity inc –> arteriolar constriction (AA and EA) –> dec RBF and constant/slight dec GFR
- 2) external baroreceptors –> RAAS system causes even more vasoconstriction of AA and EA
- 3) intrarenal baroreceptors activate
Physiological context:
- first AA constricts –> dec RBF but also dec Pgc and as a result GFR
- second EA constricts –> Pgc is restored and GFR as well but RBF dec even more
- generally GFR will still dec slightly, but not as much as RBF –> FF inc –> pigc inc –> dec GFR
Describe the role of renal prostaglandins in the renal response to hypovolemia
- produced by renal interstitial cells in kidney medulla b/w renal pyramids
- secreted in response to AT2 and have a local dilatory effect on arterioles
- 1) maintain adequate RBF by blunting effects of AT2 (renal cells are sensitive to ischemia)
- 2) focuses more on AA –> brings GFR back up to normal
What happens with severe hypovolemia in general?
- dec MAP –> 1 and 2
1) stimulate arterial baroreceptor reflex –> inc symp activity to kidneys –> constrict AA and EA (also happens through secretion of renin/AT2) –> dec RBF –> inc FF –> inc pigc and keep Pgc constant –> dec/constant GFR
2) JGA baroreceptor stimulation –> JGA renin secretion –> AT2 –> inc TPR –> restore MAP
What is filtration equilibrium?
- lose NFP as you go along glomerular capillary bed, so NFP reaches 0 at some point before plasma exits capillary
Describe the major anatomical regions of the kidney including the renal artery and vein, major and minor calyces, medulla, cortex, renal pyramids, and regions containing collecting ducts
- outer fibrous capsule
- cortex underneath capsule
- medullary pyramids under cortex
- pyramids have nephrons and collecting ducts
- collecting ducts empty urine at tips of pyramids into calyces
- minor calyx drains into major calyx into renal pelvis into hilum into ureter
- renal artery and vein are in hilum as well
Outline the flow of blood into and within the kidney finishing with its exit in the renal vein
- renal arteries come off of abdominal aorta
- in hilum, split into anterior and posterior segments –> interlobar arteries between pyramids
- near boundary between cortex and medulla, branch into arcuate arteries parallel to outer capsule
- branch into interlobula arteries in cortex to capsul
- branch into afferent artetioles that go to glomeruli of nephrons
- filter plasma contents then go into efferent arterioles
- EAs form vasa recta that surrounds tubules of nephron
- blood from peritubular capillaries and EAs –> interlobular veins –> arcuate veins –> interlobar veins –> renal vein
Describe the cellular disposition of Bowman’s capsule including the glomerulus and the cells and filtration barrier that comprise it and the visceral and parietal epithelia. Illustrate and describe the relationship between glomerular endothelial cells, the filtration barrier, the podocytes, and the mesangial cells. Why are the endothelial cells fenestrated?
- renal corpuscles are in cortex
- glomerulus is a capillary network and is surrounded by epithelial capsule called Bowman’s capsule
- you have an AA going into glomerulus and an EA leaving glomerulus
- mesangial cells is CT within capillary bed that provides support
- outside capillaries are podocytes (visceral epithelium of BC)
- basal lamina/filtration barrier between endothelium of capillaries and podocytes
- parietal epithelium of BC is simple squamous epithelium
- fenestrated endothelium prevents cells and platelets from passing
- BL prevents >65kDa sized molecules from passing, but positively charged easier to get through
- podocyte filtration is last layer of filtration; loss of podocytes –> excessive protein in filtrate
- mesangial cells are phagocytic and contractile
Describe the functions of later regions of the nephron after filtration through the glomerulus. Outline each region and give one example of specialized functions of the different portions of the nephron involved in resorption of solutes. Understand the relationship between the microscopic structure of different endothelial cells in the kidney and their function. Be able to describe where in the kidney (medulla or cortex) the different resorptive events occur
Proximal tubule:
- cuboidal epithelium and brush border of microvilli
- tight junctions between cells
- infolds on basolateral side that have Na/K ATPases to pump out Na so that Na is taken up on the lumenal side
- lots of mitochondria for ATP production
- 80% of filtrate is absorbed in this area
Loop of Henle:
- thick descending of proximal tubule –> thin loop of henle
- thin loops are simple squamous epithelium
- osmotic salt gradient maintained in medulla
- ascending loop are cuboidal cells and actively transport Na and have lots of mito and are similar to proximal tubule cells
Distal tubule:
- cuboidal and short microvilli
- acid base balance
- responde to aldosterone and ADH
- lots of mito, infolds, and ATPase for Na/K pump
Collecting tubules:
- clear cells (principal) and intercalated cells (fewer and darker)
- cuboidal cells and short microvilli and become columnar towards duct
- principal cells are active transporters and excrete K into lumen and take up Na into cell
- intercalated cells secrete H+ and reabsorb bicarb
- ADH inc permeability to H2O of collecting ducts –> more concentrated urine
Interstitial cells around tubules in medulla
- macrophages
- fibroblast-like cells
- stellate cells containing lipid droplets
- some contain mRNA for EPO production
Juxtaglomerular apparatus
- vascular pole of renal corpuscle
- connected to distal convoluted tubule through macula densa
- JG cells are smooth muscle cells in wall of AA that secrete renin
- lacis cells are in contact with macula densa and JG cells
- control BP
- response to Cl ions in urinary filtrate in distal tubules
Describe the unique epithelium of the ureters and
bladder and know its functional significance
- bladder and ureters are lined with transitional epithelium
- unique lamina propria with folded elastic CT that allows entire epithelium to stretch a lot
State the magnitude and regulated range of NaCl and water handling by the kidneys
- most of the filtered load of water and salt is obligatorily reabsorbed (a lot is filtered, little is excreted) with only a small fraction under homeostatic control
- most reabs occurs in PT and LOH
- fine tuning/homeostatically varied reabs in DT and CD
- what happens if you ingest a lot of H2O or Na? –> H2O is alright, because hard to ingest a lot of H2O, but if impaired GFR or excessive H2O reabs –> H2O intox; Na is harder because regulated/excreted amount is so small, you can exceed excretory limits –> volume expanding effect –> HTN?
Describe the major epithelial transport mechanisms for NaCl and water reabsorption in each major tubular segment
- Na/K ATPase in BL membrane –> dec Na inside cell to allow for gradient of reabs
- Cl goes through tight junctions to maintain neutrality
- H2O follows because of osmotic gradient
- glucose can be paired with Na to become concentrated inside cell
Proximal tubule: reabs majority of filtered H2O and NaCl and most of important metabolites (glucose, amino acids, bicarb)
- 65% of H2O and NaCl reabs here
- captures important metabolites at first chance
Loop of Henle:
- create a hypERtonic interstitium
- 25% of NaCl reabs in asc loop –> osmotic gradient for H2O in desc limb bc no permeability to H2O in asc limb and opposite for desc limb; 15% of H2O reabs in desc limb
- Na/K/2Cl transporter reabs Na, K, and Cl in asc limb
- very concentrated as you go towards medulla
- vasa recta also in U shape to maintain concentration gradient; h2O leaves during descent but enters in ascent and vice versa for solutes
Distal tubule/Collecting duct:
- reabs of H2O and NaCl to fine tune
- only 20% of H2O and 10% of NaCl reach
- tight junctions, so mostly transcellular movement
- ADH and aldosterone play a major role here
- aldosterone –> inc # of Na channels and BL Na pumps
- ADH/vasopressin –> aquaporins fuse into apical membrane for water to flow from lumen to serosa
State the relative proportion of water and NaCl reabsorbed in each tubular segment
PT - 65% NaCl, 65% H2O
LOH - desc: 15% H2O; asc: 25% NaCl
DT/CD - 10% NaCl, 20% H2O
Describe the overall role of each major tubular segment in the regulation of NaCl and water reabsorption
PT: Taking an obligatory “big bite” of the filtered load of H2O and NaCl, and the recapture of important metabolites in the filtrate
LOH: creation of a hypertonic interstitium
DT/CD: reabsorption of H2O and NaCl in DT/CD “fine tuning”
Identify the major hormones that regulate tubular reabsorption of NaCl and water and their tubular and cellular site of action
DT/CD:
- aldosterone –> inc # of Na channels and BL Na pumps
- ADH/vasopressin –> aquaporins fuse into apical membrane for water to flow from lumen to serosa
Describe the molecular mechanism of action of aldosterone and ADH/vasopressin with respect to NaCl and water transport
DT/CD:
- aldosterone –> inc # of Na channels and BL Na pumps
- ADH/vasopressin –> aquaporins fuse into apical membrane for water to flow from lumen to serosa
State the Starling equation for the flow of solution from the renal interstitium to the peritubular capillaries
Fic = K’ (Pint + πcap– Pcap - πint)
Give values for each of the Starling forces and the net pressure driving the flow in the Starling equation
Fic = K’ (Pint + πcap– Pcap - πint)
Pint = 7mmHg Pcap = 11mmHg - 4mmHg out of cap *Picap = 35mmHg Piint = 6mmHg - 29mmHg into cap --> NFP = 25mmHg into cap
Describe qualitatively the effects of increasing and decreasing tubular flow on water and Na excretion
- faster flow = less time to be reabsorbed = greater proportion of substances excreted
- vice versa for slower flow
- diuretic inc flow by dec H2O reabs in part of tubule –> more vol excreted
- small changes in GFR can be significant
Define “glomerulotubular balance” and “tubuloglomerular feedback” and describe the roles these processes play in the regulation of NaCl and water reabsorption
Glomerulotubular balance:
- obligatory reabsorption mechanisms in PT to compensate for changes in a filtered load
- PT adjusts to that a fixed proportion of filtered load of H2O and NaCl is always reabsorbed (65%)
Tubuloglomerular feedback:
- regulates GFR in response to changes in NaCl at macula densa, which cause AA to constrict or dilate and monitor DT
- inc GFR –> inc flow –> dec NaCl reabs in asc limb of LOH –> NaCl conc inc when reaches macula densa –> AA contracts from JGA signaling and secretion of AT2/ADH –> dec Pgc –> dec GFR
State the qualitative effects of adding and subtracting Na from the ECF on ECF volume and the physicochemical bases for these changes
- Na is the major osmotic substance in the ECF
- ECF is in osmotic equilibrium with ICF
- loss or gains in ECF Na –> changes in ECF volume more than Na conc
- injestion of 10g of NaCl to ECF ultimately results in larger inc in volume in ECF than inc in [NaCl]
- due to 2x larger vol of ICF over ECF –> Na changes in ECF leads to 2x changes in ECF volume over Na conc
Describe the physiological feedback loops involved in the homeostasis of Na balance in the ECF
- Na regulation monitor ECF volume with baroreceptors in aortic arch and carotid sinus
- RAAS and SNS activate when low ECF –> Na reabs and vasoconstriction
Feedback loop:
- dec ECF Na –> water shift from ECF to ICF –> ECF and MAP dec –> activate RAAS –> AT2 and aldosterone inc –> aldosterone inc reabs of Na
Identify the dominant pathway involved in H2O regulation during normal variations in volume and capacity
- involves sensing of serum osmolarity and modifying renal handling of water
- ECF H2O content affects ECF osmolarity/[Na] more than ECF volume
- neurons in supraoptic nucleus detect osmolarity through changes in their cell volume (ECF osm inc –> cell shrink –> secrete ADH and stimulate thirst)
- ADH levels inc when osm >280 –> osm keep inc and ADH keep inc –> more H2O reabs in DT and urine osm inc until max of 1200 –> serum osm 290 because kidneys cannot concentrate urine anymore and stimulate thirst to get more H2O
Identify the dominant pathway involved in H2O regulation during severe hypovolemia
- a state of hypovolemia, SON are stimulated and synthesize ADH
- monitoring of ECH water involves monitoring ECF osmolarity and volume
- normally, it is ECF osmolarity, but in severe hypovolemia, ECF volume overrides osmotic control
- ADH is main effector
- ECF osm inc or ECF vol severe dec –> ADH released –> ADH binds to receptor on BL side of epithelial cells in DT/CD –> synthesis of aquaporin channels on apical membrane of DT/CD cells –> permit H2O reabs –> osm of the urine inc while osm of ECF dec/vol inc
- if serum Na inc –> inc thirst and inc ADH –> inc H2O intake and inc H2O reabs
- if serum Na dec –> dec thirst and suppress ADH –> dec H2O intake and inc H2O excretion
Describe the pathways involved in the regulation of ECF volume in a hypervolemic state by atrial natriuretic factor
- inc ECF volume –> inc distention of atria –> release of ANP granule contents from atrial cardiocytes –> pro-ANP cleaved to make active ANP –> active ANP reaches target in body –> does a lot of things:
1) dec secretion of ADH/block ADH acting on tubules –> dec H2O reabs –> inc H2O excretion
2) dilates AA and EA –> inc GFR –> inc H2O excretion and Na excretion
3) dec renin release –> dec AT2 –> dec aldosterone/block aldosterone action on tubules –> dec Na reabs –> dec gradient for H2O reabs –> dec H2O reabs
Hypovolemic patient, hyper/hyponatremic
- patient is hypovolemic (losing Na) from diuretics and little food
- if also not drinking then losing H2O due to diuretics and sweating –> [Na] inc so hypovolemic and hypernatremic
- if drank a lot –> [Na] dec so hypovolemic and hyponatremic
Euvolemic hyponatremia
- patients in normal Na balance but positive H2O balance
- ADH secreted inappropriately and kidneys cannot excrete all of the water ingested
Hypervolemic hyponatremia
- seen in heart, liver, renal failure
- excretion of Na impaired –> hypervolemia
- EABV low –> ADH stimulated –> dec excretion of H2O
What happens in sever sweating?
1) dec ECF volume –> dec LA filling pressure –> inc baroreceptor reflex –> activate ADH –> inc H2O reabs
2) inc ECF osmolarity (bc losing hypotonic fluid) –> activate brain osmoreeptors in hypothalamus –> activate ADH –> inc H2O reabs
What happens in severe diarrhea?
- initial isotonic loss of ECF volume –> inc activation of ADH pathway –> inc H2O reabs
- when patient starts to recover by drinking water, drinks pure water –> overall osmolarity of ECF dec –> dec activation of ADH –> dec ADH secretion
- *changes in ECF osm are linear in ADH levels, but changes in ECF volume have no effect on ADH until volume dec significantly
- so what happens?
- first, have a severe isotonic loss, so lots of ADH secreted and osmolarity isn’t changed so no effect from there
- after drinking pure water, correct volume change back to not having an effect on ADH levels, but this reduces osmolarity and would cause a dec in ADH levels so ultimately ADH suppression occurs and excretion would be maximized
- basically:
**
ECF water regulation is primarily an osmoregulatory system with an emergency low-volume override
**
Identify the physiologic determinants of GFR at a single nephron level as well as for the whole kidney
- SNGFR is determined by Starling forces:
SNGFR = K*[(Pgc-Pt)-(pigc-pit)]
- Pgc (cap hydrostatic pressure) –> largest factor
- pigc (cap oncotic pressure)
- Pt (tubular hydrostatic pressure)
- pit (tubular oncotic pressure) –> basically zero
- K factor to account for surface area and permeability of capillary
- basically:
SNGFR prop to Pgc - Pgc influenced by AA and EA tone
- AA constr –> dec Pgc
- EA constr –> inc Pgc
- maintained by dilate AA (prostaglandins. NO) and constrict EA (AT2)
- constrict AA with NSAIDs and dilate EA with ARBs/ACEi
Identify the mechanisms operant in autoregulation of renal blood flow and glomerular filtration rate
- autoregulation is maintenance of RBF and GFR over wide range of MAP
- intrinsice to blood vessel endothelium and media
Demonstrate how to calculate and/or estimate glomerular filtration rate
GFR = Ux*V/Px
Ux = urine conc
V = urine flow rate
Px = plasma conc
- need something that is freely filtered and not reabs or secreted
- can use inulin, but need to infuse IV
- urea is freely filtered and not secreted, BUT is reabs and influenced by protein intake–> underestimation of GFR
- usually measured by creatinine –> breakdown product of muscles; freely filtered, not reabs, but secreted slightly –> overestimation by 15%, but still a fairly good measurement of GFR
Explain the concept of balance and the central role of the kidney in achieving Na, H2O, K, and acid balance
- what goes in must go out otherwise you will accumulate or the opposite
What is clearance?
- the clearance of X is defined as the volume of plasma from which all of X is removed
- if a substance is freely filtered at glomerulus and is not reabs or secreted, then its clearance = GFR
What are clinical measurement methods for GFR?
- measure plasma creatinine –> if inc, then not being excreted which indicates deteriorating renal function
**
Cr clearance = [(A)(140-age)weight]/(72Scr) - A = 1 if male, .85 if female
- age is age in years
- weight is in kg
- Scr is serum creatinine in mg/dL
- **
- can also measure using clearance:
- Clx = Ux*V/Px
- collect urine over 24hrs and get plasma creatinine
Define the pathophysiology of dec GFR in acute tubular necrosis
- vascular and tubular factors
- vascular: dec in RBF and dec in glomerular permeability
- tubular: tubular obstruction by cell debris and backleak of glomerular filtrate across incompetent tubular BM
- ischemia –> damage to tubular epithelial cells –> bare section of tubule for backleak –> cells clog up PT
What is the definition of acute kidney injury?
- a rapid reduction in GFR leading to an inc in plasma creatinine conc, urea, and other nitrogenous wastes leading to azotemia
- three types:
1) pre-renal: dec in GFR due to dec in renal plasma flow/perfusion
2) post-renal: dec in GFR due to obstruction of urine flow
3) intra-renal: dec in GFR due to direct injury to kidneys
What is uremia?
- multiple organ dysfunction due to retention of “uremic toxins”, lack of renal hormones, due to acute/chronic kidney injury
- symptoms include NVD, abd pain, weakness, fatigue
Prerenal azotemia
- reduction in renal perfusion
- 60-70% of AKI cases
- try to restore intravascular volume to prevent ischemic injury
- prolonged prerenal azotemia may leads to ATN
- dec ECF vol: renal losses, GI losses, hemorrhage
- inc ECF vol –> dec CO (CHF, MI, etc.) or systemic arterial vasodilation (cirrhosis, sepsis, etc.)
- FENa is less than 1% with prerenal azotemia because Na reabsorbed a lot and Cr conc will be high
- treat by optimizing renal perfusion (improve CO in CHF or giving fluids)
What is the fractional excretion of Na?
FENa = CNa/Cr * 100
- UNa/PNa / UCr/PCr * 100
Postrenal azotemia
- usually due to obstruction of urine flow
- inc in intratubular pressure causes low GFR acutely
- impairment of tubular Na reabs –> inc urine Na conc and low urine Cr conc
- FENa usually >2%
- check with renal ultrasound
- catheter can diagnose and treat at the same time
- prompt relief of acute obstruction is usually assoc with complete return of renal function, but prolong obstruction is often accompanied by incomplete return of renal function
- treat with relief of obstruction
Intrarenal azotemia
- 4 types:
1) vascular: cholesterol emboli, renal vein thrombosis
2) glomerular: acute GN, hemolytic uremic syndrome
3) interstitial: acute interstitial nephritis
4) tubular: ischemia, ATN
What is the clinical approach to AKI?
1) history and physical exam:
- intravascular vol depletion –> pre-renal
- cardia dysfunction –> pre-renal
- hypotension, surgey, hemorrhage, transfusion reactions, radiocontrast dye, cardiac cath –> can indicate ATN
- urinary obstruction
- rash, fever, etc.
2) urinalysis:
- high tonicity if reabs H2O –> pre-renal
- heme pigments without RBCs –> rhabdomyolysis or hemolysis
- RBC casts –> GN
- WBC casts –> AIN (allergic interstitial nephritis)
- pigmented, granular casts and renal tubular epithelial cells –> ATN
3) urine chemistries:
- low FENa –> prerenal
- high FENa –> other causes
What is the definition of nephrotic syndrome?
- excessive leak of protein through glomerular capillary into urinary space
- > 3.5g/day of albuminuria –> hypoalbuminemia and edema
- hyperlipidemia (inc serum cholesterol)
- lipiduria (fat in urine)
1) Proteinuria (>3.5g/day):
- disruption of slit diaphragm
- nephrin defect, injury to podocyte
2) Hypoalbuminemia (serum albumin less than 3g/dL):
- proteinuria and inc catabolism of reabs protein in tubules
- liver inc protein synth but cannot compensate completely
3) Edema:
- dec serum albumin –> dec capillary oncotic pressure –> inc fluid in intersititium
4) Hyperlipidemia (cholesterol >250mg/dL):
- inc in serum cholesterol due to inc lipoprotein synth of liver
5) Lipiduria:
- inc capillary wall permeability and hyperlipidemia
- “maltese cross”
also see:
- inc risk of infection due to loss of IgG and complement in urine; pneumonia and bacterial peritonitis
- inc thrombosis risk due to inc in coag factor synth
- poor growth due to loss of vitamin D
- protein malnutrition
What is the definition of nephritic syndrome?
- active inflammation within glomerulus leads to damage to the glomerulus with subsequent loss of filtration and a dec DFR
presents with:
- microhematuria, leukocyturia, occasionally red cell casts, non-nephrotic proteinuria, dec GFR, HTN, edema
What are the major nephrotic syndrome diseases? both renal-only and systemic
Renal only:
- hereditary nephrotic syndrome
- minimal change disease
- focal segmental glomerular sclerosis
- membranous nephropathy
- membranoproliferative GN
systemic:
- diabetes
- amyloidosis
- light chain deposition disease
- lupus membranous type
What are the major nephritic diseases? both renal-only and systemic
Renal only:
- post strep GN
- IgA nephropathy
- rapidly progressive GN (anti-GBM nephritis, idiopathic RPGN)
systemic:
- ANCA-assoc vasculitis
- microscopic polyangiitis/granulomatous polyangiitis
- henoch-schonlein purpura
- HCV-assoc cryoglobulinemia
- SLE
Minimal Change Disease
Definition:
- common cause of nephrotic syndrome
- glomeruli appear normal under light microscopy
Epidemiology:
- 75% of cases in children
Pathology:
- normal LM
- no complement on IF
- EM find foot process fusion
Etiology:
- due to circulating permeability factor produced by T cells –> acts directly on podocyte –> disruption of filtration barrier leads to inc permeability
Presentation:
- nephrotic syndrome
- edema and weight gain
- normal GFR
- no HTN
- usually occurs with viral URTI
Treatment:
- steroids
- maybe add cyclophosphamide if relapses
Overall good prognosis
Hereditary Glomerular Disease
Etiology:
- mutations in nephrin, podocin, and WT-1
Presentation:
- steroid-resistant nephrotic syndrome
- nephrin mutation leads to proteinuria, edema, and failure to thrive
Pathology:
- lesion is similar to FSGS
Treatment:
- reduce proteinuria with ACEi and eventually renal transplant
What happens in asymptomatic proteinuria and/or hematuria?
- > 150mg protein/day
- selective or nonselective (loss of size barrier; more common)
- can lead to nephrotic syndrome
- RBC casts specific for glomerular bleeding
Focal Segmental Glomerular Sclerosis (FSGS)
Definition:
- LM shows normal appearance except segmental scarring in some glomeruli
- proteinuria caused by rest of glomeruli where capillary wall shows inc permeability
Epi:
- common in AfAms and 20-40yos
Pathology:
- segmental scarring in some glomeruli
- IF is usually negative but can show IgM and C3 in scarred areas
- EM shows diffuse foot process fusion with generalized capillary wall defect
Etiology:
- idiopathic FSGS caused by circulating factors that affects podocyte
- genetic mutations to podocin gene
- HIV nephropathy –> lesion of FSGS
- AfAms have polymorphisms in apoliprotein that provide protection against trypanosomiasis
- assoc with minimal change disease or heroin use or HIV infection
Presentation:
- idiopathic nephrotic syndrome
- maybe HTN or microhematuria
Treatment:
- reduce proteinuria with ACEi –> dec glomerular pressure
- corticosteroids can help and cyclosporines
- antiretroviral for HIV patients helps
Can progress to renal failure
Membranous Nephropathy
Definition:
- immune mediated with immune complex deposition in subepithelial space (between podocyte and GBM)
- GBM appears thickened under LM
Epi:
- most common cause in older adults
Pathology:
- thickening of GBM by LM
- spikes along BM after staining –> extensions of new BM material between immune complex deposits on subepithelial side of BM
- IF shows granular deposits of Ig and C3 along GBM
- EM shows electron dense subepithelial deposits of immune complexes
Etiology:
- autoimmune but antibody against antigen on podocyte (PLA2 receptor) –> complement/immune complex injury to podocyte –> capped and shed into subepithelial space and forms deposit
- assoc with hep B, lupus, drugs, and cancer
Presentation:
- nephrotic syndrome
- can have non nephrotic proteinuria early on
- HTN and renal failure can develop over time
- look for cancer
Treatment:
- steroids
- cytotoxic drugs (cyclophosphamide)
- ACEi to lower proteinuria
Membranoproliferative Glomerulonephritis (MPGN)
Definition:
- proliferation and thickening of GBM
- type 1 = immune complex deposition
- type 2 = complement activation in capillary wall w/o immune deposits
Epi:
- type 1 assoc with chronic hep c virus
- type 2 seen with defects in alternative complement pathway
Pathology:
- LM shows thickening of GBM, mesangial cell proliferation, lobulated glomerulus
- deposits of C3 and IgG prominent on capillary walls, mesangium,
- type 2 is similar but just not IgG
Pathogenesis:
- nephrotic/nephritic
- trapping of immune complexes in subendothelial and mesangial areas –> complement activation and leukocyte recruitment
- circulating nephritic factor
Presentation:
- acute nephritis
- HTN
- hep c infection
Treatment:
- anti HCV therapy
- immunosuppression
- steroids
Diabetic Nephropathy
- glycosylation of GBM inc permeability and thickening
- mesangial expansion from dec turnover of glycosylated proteins in mesangial matrix
- inc glucose (inc TGF)
- EA glycosylated (inc GFR)
- hyperfiltration injury
- *proteinuria –> nephrotic syndrome
- microhematuria, but no casts
- eosinophilic nodular GS, mesangial expansion, GM thicken
- control blood glucose and HTN via ACEi
SLE / Lupus nephritis
- endogenous Ab-Ag complex from ANAs
- nephritic presentation
- but also nephrotic
- treat with steroids
Pathology:
- immune complexes in mesangium, subendothelial space, subepithelial space
- IF shows C3, IgC, IgM, IgA, and C1q
- lumpy bumpy
Pathogenesis:
- autoantibodies to DNA, RNA, histone
Presentation:
- proteinuria, hematuria
- can be nephritic or nephrotic
Treatment:
- high dose corticosteroids
Amyloidosis
- multiple myeloma, TB, RA
- nephrotic syndrome
- systemic symptoms (enlarged spleen/liver, CHF, etc)
- look for plasma light chains
- amyloid deposits in renal biopsy
- congo red stain shows apple green birefringence
What happens in nephritic syndrome?
- hematuria
- dysmorphic RBCs
- RBC casts
- proteinuria
- HTN and edema
- dec GFR (inc serum Cr)
- RBCs, WBCs in urine
- inflammation of glomeruli
- orthopnea
- pulm edema
Clinical evaluation of suspected GN
- history and PE focus on rashes, lung disease, neuro problems, viral/bact infections, MSK or heme abnormalities
- labs: get a CBC, electrolytes, 24hr urine, LFTs
- serum complement levels
- tissue diagnosis
Pathophysiology of nephritic syndrome
- glomerular inflammation
- cells/casts in urine
- immune complexes deposit in mesangium or subendothelial space –> inflam mediators and bring in inflam cells
- auto-antibodies can cause glomerular endothelial injury
- ANCA mediate vasculitis causes necrotizing injury of glomerular capillaries
1) proteinuria:
- direct damage to glomerular capillary wall by immune mechanisms –> inc in protein filtration
- usually less than 3g/day (contrast to nephrotic syndrome)
2) dec GFR:
- acute inflammation –> vasoconstriction/occlusion/thrombosis of cap loops –> dec surface area
- azotemia
- hyperkalemia
3) urine sediment:
- RBCs, WBCs, RBC casts –> glomerular inflammation and disruption of GBM
4) edema:
- inc in reabs of Na and H2O due to dec glomerular perfusion –> inc ECF volume
5) HTN:
- Na and H2O retention
What is seen on histology of glomerulonephritis?
LM:
- look at glomeruli for hypercellularity, scarring, lesions
- crescents if proliferation of cells in BC (macrophages and parietal epithelial cells) –> RPGN
IF:
- if Igs present or complement proteins
EM:
- morphology of BM
- fusion of podocytes (nephrotic syndrome)
- immune deposit locations
Post-infectious Glomerulonephritis
- usually after group A strep infection; maybe after staph endocarditis
Epi:
- 2-3wks after infection
- can also occur with acute endocarditis
Etiology:
- antibody response to certain streptococcal antigens –> immune complexes lodging in flomeruli –> activating of complement
Pathology:
- LM shows proliferation with infiltration of neutrophils and monocytes
- IF shows *granular deposits of IgG and C3 in subendothelial, mesangial, and subepithelial areas;
- EM shows subendothelial and mesangial deposits and *“subepithelial humps”
- Cr and BUN inc
- WBC mild inc
Presentation:
- edema, weight gain
- hematuria, proteinuria
- dec GFR
- HTN
- inc antibodies to strep antigens
- inc alternate complement pathway (low C3, high C4)
- pulm edema (rales)
- fever
Diagnosis:
- nephritic snydrome
- positive streptozyme test
- low C3 levels
- if severe or persistent, get biopsy
- IF shows burning bush
Treatment:
- self-limiting; maybe steroids
IgA Nephropathy
- mesangial proliferative GN with IgA immune deposits in mesangium, but not so much in subendothelial areas
Epi:
- most common acute GN; 15-35yos
Etiology:
- IgA immune complexes in mesangium –> proliferation and matrix expansion
Pathology:
- LM shows inc in mesangial cells
- IF shows IgA, IgG, C3 in mesangium
- *burning bush on IF = mesangial IgA, C3
- EM shows mesangial immune deposits
Presentation:
- *asymptomatic microhematuria –> nephritic syndrome
- nonnephrotic proteinuria
- ok renal function
- occasional RBC casts
- onset of viral illness
- occasional fever, rash, GI issues, renal disease
- skin biopsy shows IgA deposits (Henoch Schonlein purpura)
Treatment:
- 25-50% progress to ESRD over 15yrs
- ACEi can slow progression
- steroids may help
Anti-GBM disease / Goodpasture’s syndrome / Rapidly Progressive (Crescentic) GN
- sever GN with pulm hemorrhage
- goodpastures = pulm hemorrhage, Fe deficiency anemia, GN due to circulating antibody to GBM
Pathology:
- antibody to collagen in GBM –> IgG deposits by IF
- complement activation
- neutrophil infiltration
- crescent formation and loss of renal function (RPGN)
*** IF: - linear = goodpastures, anti-GBM - granular = IgA, SLE, endocarditis - no staining = GPA ***
Presentation:
- rapidly progressive GN
- high fevers, nausea, vomiting, hemoptysis
- oliguria
- pulm hemorrhage from antibody deposition on alveolar BM
- smoking makes worse
- can be renal only
- anti-GBM antibodies detected using ELISA
Treatment:
- aggressive steroids
- immunosuppression
- plasma exchange
- kidney biopsy
Pauci-Immune Renal Vasculitis
- small vessel vasculitis of kidneys without evidence of immune complex deposition
Pathology:
- glomeruli demonstrate fibrinoid necrosis and crescents
Pathogenesis:
- anti-neutrophil cytoplasma antibodies (ANCA)
Presentation:
- multiple organs affected
- nephritic pattern of renal disease
- alveolar capillaritis and pulm hemorrhage
Treatment:
- immunosuppressive drugs
- steroids and cyclophosphamide
- plasma exchange
Cryoglobulinemia
- antibodies that ppt in cold –> immune complexes in small vessels –> vasculitis
Epi:
- hep c infection
Pathology:
- immune complex GN
- membranoproliferative pattern; subendothelial deposits
Pathogenesis:
- hep c infection
Presentation:
- palpable purpura
- arthralgia
- general weakness
- proteinuria, hematuria
Treatment:
- antiviral for hep c
- rituximab
Henoch Schonlein purpura
- skin lesions/palpable purpura
- arthritis
- GI involvement (colic and bleeding)
- GN
- focal proliferative necrotizing GN
- crescents
- mesangial and cap wall IgA deposits
Chronic Renal Failure
- nephron loss –> dec GFR
- uremia
- due to glomerular disease, vascular disease/HTN, infection, drugs, urinary tract obstruction
Define focal, diffuse, segmental, and global
- focal = few glomeruli
- diffuse = all glomeruli
- segmental = part of a single glomerulus
- global = all of a single glomerulus
Alport’s Disease
- nephritis, deafness, ocular lesions
- mutation of collagen IV
- X-linked
Define the basic principles of urine collection
- 1-2L/day of urine produced usually
- must be tested w/in 2hrs of collection
- refrigerate if can’t be examined w/in 2 hrs
- 24hr specimens are not acceptable for testing
- 24hr collection with container using preservatives
Describe the different types of urinalysis and understand their corresponding clinical-pathological correlation, including macroscopic examination and chemical analysis (use and interpretation of dipstick for: glucose; bilirubin; specific gravity; blood; pH; protein; urobilinogen; nitrite; leukocyte esterase; microscopic examination; and cytology)
Visual Inspection
1) volume
- polyuria = >2L/day; indicates defective reabs of Na/H2O
- oliguria = less than 500mL/day; indicates pre, infra, post renal disease
- anuria = less than 100mL/day
2) color
- yellow, green, brown: bile pigments (bilirubin)
- orange, red, brown: excreted urobilinogen
- pink, red: hematuria
- dark brown, black: methhemoglobin, rhabdo
3) turbidity = undissolved solid material (cells/crystals)
Chemical Screening
1) specific gravity:
- kidney’s conc ability
- less than 1.001 –> less conc; polydipsia, diuretics, DI
- >1.035, more conc; dehydration, DM, proteinuria, CHF, addison’s, SIADH
- osmolality is normally 500-850mOsm/kg
- if acute oliguria and >1.01 = pre-renal; if 1.008-1.012 = RTA
2) pH:
- 4.6-8
- acidic = met/resp acidosis, high protein diet,
- alkaline = RTA, UTI, excess bicarb ingested, met/resp alkalosis
3) proteinuria:
- usually less than .5g/day in urine
- nephrotic syndrom (>3.5g/day) or multiple myeloma if proteinuria
- proteinuria = >150mg/dL
4) glucose:
- normall undetectable in urine
- w/ hyperglycemia, glucose appears in urine when blood glucose >180-200mg/dL
5) ketones:
- positive in urine when inc in lipid metabolism
6) blood:
- no RBCs = free Hb = intravascular hemolysis
- RBC casts = glomerular hematuria = if renal dysfunction, then nephritic syndrome
- free RBCs = non-glomerular hematuria = kidney, ureter, bladder, urethra
7) nitrite:
- indicates UTI; usually gram neg bacteria
8) leukocyte esterase:
- made by neutrophils
- can indicate UTI, vaginal secretion, or glomerulonephritis
Microscopic Examination
- > 3 RBCs/HPF is abnormal
- dysmorphic shape = glomerular origin (usually w/ RBC casts)
- normal shape = non-glomerular pattern w/ no casts
- > 5 WBCs/HPF is abnormal (inflammation)
- renal tubula epithelial cells shed during renal parenchymal disease (+ lipid = nephrotic syndrome)
- hyaline casts: dehydration, fever, renal injury (lots) but otherwise nonspecific
- waxy casts: advanced chronic renal failure
- RBC casts: glomerular disease
- WBC casts: inflammation in kidney
- tubular cell casts: ATN, virus, drugs/toxins
- granular casts: immune complexes, fibrinogen
- fatty casts: nephrotic syndrome
Understand that hypo/hypernatremia refer to the concentration of Na in serum and not to the absolute amount of Na in the body
- concentration, so relative amounts of Na and H2O
- hyponatremia is most commonly caused by excess of H2O (ADH)
Describe the pathophysiology of how hypo/hypernatremia can developed (importance of ADH)
- hyponatremia is most commonly caused by excess of H2O due to release of ADH
- tonicity of ECF reflects tonicity of cells
- serum osm = 2*Na + BUN/2.8 + glu/18
What are the 3 essential features of a normal diluting system?
1) tubular fluid is diluted in ascending LOH and DT by reabs of NaCl; Na/K/2cl contransporter in asc limb and NaCl cotransporter in DT
2) normal GFR and proximal reabs; if inc proximal reabs –> dec DT delivery –> vol of dilute urine excreted dec
* 3) absence of ADH; if ADH, then CD becomes H2O permeable –> lumen and interstitium equilibrate –> urine becomes concentrated (H2O leaves to interstitium) so dec H2O excretion
What are the 3 essential features of a normal concentrating system?
600mOsm waste needs to be excreted –> can be as little as .5 L if concentrating ability is ok
1) generate a hypertonic interstitium; asc LOH w/ Na/K/2Cl contransporter makes interstitium hypertonic and dilutes tubular fluid
2) secretion of ADH; CD permeable to H2O –> water reabs to make urine concentrated
3) if can’t concentrate, then need to excrete more volume of urine –> need to replace these H2O losses
When is ADH released?
- change in serum osm (high) and changes in effective intravascular blood volume (low)
- initially controlled by inc osm but when volume depletion is really severe, then blood volume response dominates
- aka normally osmoregulatory, but during stress becomes volume regulatory
How does ADH work?
- ADH reacts with tubular cell membrane receptor –> activates adenylate cyclase –> cAMP –> cascade resulting in aquaporins to reabs H2O
What happens in hyponatremia, generally?
- bad at excreting H2O –> retain a lot of H2O –> ECF volume inc –> dilute serum Na –> hyponatremia
What are the 3 different types of hyponatremia?
- hypertonic (>300mOsm serum osm)
- isotonic (280-300mOsm serum osm)
- hypotonic (less than 280 mOsm serum osm)
Hypertonic hyponatremia
- inc in non-Na solute –> hyperglycemia, mannitol, glycerol
- inc glucose 100 mg/dL = serum Na dec 1.6 mEq/L
- high Sosm –> H2O shifts from ICF to ECF –> hypertonic hyponatremia
Isotonic hyponatremia
- normal Sosm
- lab artifact caused by hyperlipidemia or hyperproteinemia (multiple myeloma)
Hypotonic hyponatremia
- 3 types: hypervolemic, euvolemic, hypovolemic
- hypervolemia: edema
- hypovolemia: high serum uric acid; hypotension, tachycardia, orthostasis)
- euvolemia: low serum uric acid
Hypovolemic hyponatremia
- low total body Na
- appropriate ADH release causes reabs of H2O to help ECF volume depletion
- causes can include: GI losses, diuretic use, salt losing nephritis, mineralocorticoid def, osmotic diuresis
- treat with normal saline
- if UNa > 20 –> renal loss (not reabs Na)
- if UNa less than 20 –> extrarenal loss
Hypervolemic hyponatremia
- high total body Na
- seen in CHF, cirrhosis, nephrotic syndrome –> EABV is dec (poor perfusion) –> ADH activation
- renal failure –> inability to lose free H2O due to dec GFR
- see edema
- caused by CHF, cirrhosis, nephrotic syndrome, and advanced/chronic/acute renal failure
- if UNa >20 –> ARF, CKD (kidneys not reabs Na)
- if UNa less than 20 –> CHF, cirrhosis, nephrotic syndrome
- treat underlying cause with loop diuretics
Euvolemic hyponatremia
- normal total body Na
- inc ADH secretion but no inc in Sosm or dec EABV (inappropriate)
Causes can include:
- hypothyroidism –> ADH secretion
- drugs
- adrenal insuff
- primary polydipsia (excessive thirst)
- SIADH (hypoosmolality, non-dilute urine and non CV, hepatic, renal disease) caused by carcinomas, pulm diseases, CNS disorders
What are signs of hyponatremia?
- GI issues (anorexia, nausea, vomiting)
- altered sensorium
- seizures
How do you treat hyponatremia?
- restrict H2O
- correct underlying disease
- give hypertonic NaCl with/out furosemide (which inc free H2O excretion)
- raise the serum Na slowly to avoid neuro problems (central pontine myelinolysis)
When does hypernatremia occur?
- ADH is dec or ineffective
- H2O intake is less than required to compensate for GI losses
- common causes are dec thirst, inability to obtain water
- see inc in Sosm
What are the causes of hypernatremia?
- dec total body Na –> body water loss > body salt loss –> GI loss, burns, diuretic use w/o water intake
- inc total body Na –> rare; hypertonic fluid received
- normal total body Na –> either ADH def (central DI) or ADH resistance (nephrogenic DI)
Describe the causes of hypernatremia with normal total body Na
Central diabetes insipidus
- ADH deficiency
- usually idiopathic, maybe head trauma, surgery, neoplasma
- treat with ADH (DDAVP)
Nephrogenic DI:
- ADH resistant (renal duct is unresponsive)
- congenital (rare) or acquired from CKD, hypercalcemia, hypokalemia, drugs, sickle cell anemia, polycystic kidney disease, urinary obstruction; pregnancy release of vasopressinase
- does NOT respond to ADH –> treat with lots of fluids and thiazide diuretics (dec urine flow by causing Na loss and volume depletion)
What are signs of hypernatremia?
- neuromuscular irritability (twitches, hyperreflexive, seizures, coma, death)
How do you treat hypernatremia?
- restore Sosm to normal
- give water according to .6weight[(current Na/140)-1]
- give water slowly to avoid sudden shifts in brain cell water
Discuss the concept of EABV and the hormonal mechanisms involved in its maintenance. Must also understand how these systems interact when one (or several) components are diseased
- EABV is the vol of blood detected by volume sensors in arterial circulation
- afferent limb detects changes in EABV and efferent limb regulates rate of Na excretion
Describe the distribution of the total body water
- 42L TBW
- 2/3 (28L) ICF
- 1/3 (14L) ECF
- out of 14L ECF –> 10.5 is extravascular, 3.5 is intravascular
What are the volume sensors?
1) low pressure baroreceptors
- cardiac atria, LV, pulm vasculature
- venous side
- protect against ECF vol expansion and contraction
- inc vol –> inc venous return –> stretch receptors signal hypothalamus and medulla –> dec renal SNS activity –> dec Na and H2O (excreted) –> dec ECF vol
2) high pressure baroreceptors
- carotid sinus
- aortic body
- arterial side
- protect against vol depletion
- dec EABV –> signal brain –> inc renal SNS activity –> retain Na and H2O –> inc ECF vol
- also release NE –> inc BP by inc HR and TPR
3) intrarenal sensors
- in JGA
- release renin
- dec in arterial pressure –> inc in intracellular Ca –> inc in renin secretion –> Na reabs with aldosterone
What are factors that regulate renal Na excretion?
1) GFR
- 23g usually filtered/hr
- autoregulated
- TGF: inc distal delivery of NaCl –> inc AA tone –> RBF and GFR dec
- GTB: changes in GFR = change in rate of PT Na reabs so that it stays ~65%
2) PT physical forces
3) Humoral effector mech
- vol dec –> AT2, aldosterone, and catecholamines retain Na
- vol inc –> PGs, BK, ANP excrete Na
4) Renal symp nerve
- vol dec –> retain Na and release renin
What parts of the nephron handle Na?
1) proximal tubule
- PT reabs ~60% of Na
- electrochemical gradient to go inside cell maintained by Na/K ATPase
- coupled to Cl, PO4, glucose, amino acids, etc.
- Na/H antiporter brings Na in and H out
2) LOH
- 30% Na reabs in thick asc limb, which is impermeable to H2O
- Na/K/2Cl transporter (loop diuretics block) brings into cell caused by Na/K pump gradient
3) DT
- 1) Na enters cell through Na channels (amiloride blocks) and Cl ions go between cells
- 2) NaCl reabs occurs by NaCl cotransport (thiazides block)
- 3) Na goes in and H goes out
4) CD
- intercalated cells secrete H (A) and bicarb (B)
- Na enters principal cells (amiloride blocks) and K leaves
What are the causes of extracellular volume contraction?
- renal or extra-renal
- renal: salt and water loss due to loss of effector mechanism (diuresis, adrenal insuff, aldosterone def, Na transporter defects) or intrinsic renal disease
- extra-renal: GI loss, skin, hemorrhage, accumulation into areas outside ECF and ICF
What are Bartter’s and Gitelman’s syndrome?
- they are renal losses of Na and H2O
- Bartter’s: mutation in Na/K/2Cl cotransporter in TALOH; hypokalemia (K is excreted), hypomagnesemia, metabolic alkalosis, inc renin and aldosterone, inc Ca excretion, and normal BP (kind of like loop diuretics)
- Gitelman’s: mutation in NaCl cotransporter in DT –> hypokalemia, hypomagnesemia, metabolic alkalosis, dec urine Ca
What are extrarenal losses of volume?
- when extra renal loses are not replaced
- vomiting, nasogastric suction –> metabolic alkalosis
- diarrhea –> loss of bicarb = metabolic acidosis
- excessive sweating –> loss of hypotonic fluids
What is the physiologic response of the body to ECF volume depletion?
- baroreceptors detect dec EABV –> inc SNS activity –> inc HR, inotropy, TPR; also inc AT2, ADH, and endothelin
- renal response is to replenish fluids and conserve salt
- dec GFR = dec Na filtered/inc reabs of Na
- activate renal SNS –> constrict AA (dec GFR) = inc reabs of Na
- inc oncotic pressure/dec hydrostatice pressure = inc fluid reabs into vessels
- RAAS –> AT2 acts on Na/H in PT to inc Na reabs; aldosterone in DT creates more Na/K pumps to reabs more Na
- ADH = inc H2O reabs
- ANP = inc Na reabs
What shows up on history and PE for volume depletion?
- thirst, postural dizziness, weakness –> mild
- worsened lightheadedness/dizziness –> severe
- palpitations
- dec urine output
- confusion
- orthostatic hypotension
- tachycardia
- dry mucous membranes
- hypotension
- dec RA pressure and CVP and LA pressure
- dec CO
What serum values show up in volume contraction?
- inc BUN/Cr ratio –> normally 10-15:1; if vol dec –> kidney reabs Na in PT –> urea follows Na –> BUN inc
- metabolic alkalosis if vomiting
- metabolic acidosis if diarrhea
- inc hematocrit and serum albumin
What urine values show up in vol contraction?
- UNa is low because trying to reabs Na
- if UNa is high, then probably ATN or kidney damage leading to inability to reabs Na
- FENa = UNa/PNa / UCr/PCr * 100; less than 1% if prerenal azotemia, >2% if acute renal failure
- Sosm inc –> kidney reabs Na and H2O to produce concentrated urine
- Sosm dec –> excrete free H2O to produce dilute urine
