Week 1 Flashcards
1
Q
What are the two differences between the right and the left kidney?
A
- Right and left differences
- Right kidney is lower than left due to the liver
- Right kidney is less protected by the ribs than the left because it is lower
2
Q
Where do the ureters lie in relation to the transverse processes?
A
- Ureters run anterior to the lumbar transverse processes and sacrum
3
Q
- Compare the sizes of the L and R renal artery and renal veins. Why are they different sizes?
A
- IVC is more right and aorta is more left
- Therefore, right renal vein is shorter than left renal vein; and right renal artery is longer than left renal artery
4
Q
What two structures are the kidneys closest to? When is it important to be aware of this?
A
- Kidney are close to vital structures like the lung and liver – necessary to be aware of when trying to biopsy the kidney
5
Q
What space are the kidneys, ureters, and the abdominal portion of the ureters in?
A
- The kidneys, ureters and the abdominal portion of the ureters are considered retroperitoneal organs. The retroperitoneum is extraperitoneal.
6
Q
What are the two descriptors for organs in the abdominopelvic cavity (in terms of location?
What are the three spaces of the retroperitoneum called?
A
- The organs of the abdominopelvic cavity are described as being either intraperitoneal or extraperitoneal.
- The retroperitoneum is made up of three spaces, the perinephric (perirenal) space and the anterior and posterior paranephric (pararenal) space.
7
Q
What are they yellow arrows pointing to?
A
- The kidney organ is surrounded by the perinephric fat which is surrounded by the perinephric fascia (yellow arrows) separating it from the paranephric space
8
Q
Know these spaces.
A
Know them.
9
Q
Label 1-4 (stages of contrast)
A
- Imaging – ability to access to physiology
- Non-Contrast (1)
- 0 seconds: normal, baseline
- Contrast enhanced
- Corticomedullary phase (2)
- 25-80 seconds: Cortex is enhanced
- Nephrographic phase (3)
- 80-150 seconds: enhances the cortex to medulla transition
- Pyelographic (excretory) phase (4)
- 3-15 minutes: hilum is enhanced
- Corticomedullary phase (2)
- Non-Contrast (1)
10
Q
What is the route that urine takes in a nephron starting at the glomerulus?
A
- Glomerulus → Bowman’s capsule → Proximal convoluted tubule (PCT) → Loop of Henle → Distal convoluted tubule (DCT) → Collecting Duct
11
Q
What are the two parts of the nephrons and what parts of the nephron are part of each one?
A
- Two parts of nephron
- Renal corpuscle – filters blood plasma
- Glomerulus – capillary network
- Bowman’s capsule – surrounds glomerulus
- Located in the renal cortex
- Renal tubule – filtered fluid passes into
- PCT
- Descending and ascending loop of Henle
- Located in the renal medulla
- DCT
- Renal corpuscle – filters blood plasma
12
Q
What are the types of cells in the following:
- Proximal convoluted tubule
- Descending limb of loop of Henle
- Ascending limb of loop of Henle
- Distal convoluted & collecting ducts
A
- Proximal convoluted tubule
- simple cuboidal with brush border microvilli
- Descending limb of loop of Henle
- simple squamous
- Ascending limb of loop of Henle
- simple cuboidal to columnar
- forms juxtaglomerular apparatus where makes contact with afferent arteriole
- Macula densa
- Distal convoluted & collecting ducts
- simple cuboidal to columnar, principal & intercalated cells which have microvilli
13
Q
What are the parts of the glomerular filtration barrier (inner to outermost)?
A
- Innermost to outermost
- Capillary endothelial cells –fenestrations covered by a thick glycocalyx (negative charge)
- Basement membrane
- Lamina rara interna – under the capillary endothelium; rich in polyanions
- Lamina densa – middle layer, contains collagen type IV, acts as physical barrier
- Lamina rara externa – supports podocytes - rich in polyanions
- Visceral epithelial cells (podocytes) – filtration slits covered by slit membranes, between interdigitating foot processes (pedicels)
14
Q
What is this showing?
A
Glomerular filtration barrier
15
Q
What is the blood supply of the kidney from the renal artery to the renal vein?
A
- Renal artery → segmental artery → interlobar artery → arcuate artery → interlobular artery → afferent arterioles → glomerular capillaries → efferent arterioles → peritubular capillaries → interlobular veins → arcuate veins → interlobar veins → renal veins
16
Q
What structure is shown and what does it contain (RC)?
A
Renal cortex containing renal corpuscles
17
Q
What structure is shown on the lower half of this picture and what part of the nephron lies in this area?
A
Renal medulla and contains the loop of henle
18
Q
What structure is shown on the lower half of this picture and what part of the nephron lies in this area?
A
Renal corpuscle made up of Bowman’s capsule and the glomerulus
19
Q
Where vascular pole and between what two structures does it sit?
A
High density cells between the macula densa (MD) and the glomerulus
20
Q
What is shown here and what kind of cells is it lined by?
A
Proximal convoluted tubule is lined with small cuboidal cells with microvilli brush border
21
Q
What kind of cells is the DCT lined by?
A
Larger cuboidal cells without microvilli brush border
22
Q
What is the arrow pointing too and where is this located?
A
- Macula densa
- Transition section between ascending loop of Henle and the DCT
- Located betwen afferent and efferent arterioles
23
Q
What part of nephron is shown here and what two cells is it made up of?
A
- Collecting duct
- Made up of principle cells (light cells) and interacalated cells (dark cells)
24
Q
What is the fuzzy blue stuff between each renal corpuscle? What is the darker blue stuff in the middle?
A
- Mesangial cells
- Fuzzy blue stuff between each renal corpuscle; dark blue areas are the nuclei
25
Define deformation and give renal examples.
* Deformation - abnormality of morphogenesis due to extrinsic factors of development
* Club foot due to Potter sequence
26
Define disruption and give renal examples.
* Disruption – destructive forces (teratogens, anoxia, infections) acting upon normal developing structures
* Missing digits or limbs
27
Define malformation and give renal examples.
* Malformation – abnormality of morphogenesis due to intrinsic factors of development
* Renal agenesis
28
Define hereditary and give renal examples.
* Hereditary – inherited genetic mutation
* Autosomal dominant polycystic kidney disease (ADPKD)
29
Define congenital and give renal examples.
* Congenital – developmental abnormality
* Uretero-pelvic junction obstruction, bladder exstrophy
30
How can a baby get club foot from renal agenesis?
* Renal agenesis → lack of urine → reduction in amniotic fluid → compression of limbs → club foot
31
What is multicystic renal dysplasia and what two things is characterized by?
* Multicystic renal dysplasia
* Congenital malformation characterized by cysts and abnormal tissue resulting in malformed kidney and obstruction of lower urinary tract
* Characterized by heterologous cartilage and swirling stroma around cyst
* Can be either unilateral or bilateral (b/c congenital and not genetic)
32
What disease is shown?
Multicystic renal dysplasia
33
For adult polycystic kidney disease:
* What is the general prognosis?
* Complications?
* Pathology?
* Adult PCK
* Prognosis: progressive disease leading to significant loss of renal function in late adulthood
* Complications: asymptomatic hepatic cysts, cerebral aneurysms, common cause of death due to cardiac complication of chronic renal failure
* Pathology: increased size of kidney with flattened cuboidal epithelium lining cysts
34
For childhood polycystic kidney disease:
* Prognosis?
* Complications?
* Pathology?
* Childhood PCK
* Prognosis: very unlikely to survive infancy
* Complications: portal hypotension caused by congenital hepatic fibrosis
* Pathology: cysts perpendicular to kidney surface
35
For childhood polycystic kidney disease:
* What kind of hereditary trend does the mutation have?
* What is the mutation in?
* What is the general epidemiolgy?
* Is it unilateral or bilateral?
* Childhood PCK
* Autosomal recessive
* Mutations: PKHD1 – encodes fibrocystin expressed in kidney and liver
* Cell differentiation in liver/kidney ducts
* Epidemiology: children, rare
* Always bilateral because hereditary
36
For adult polycystic kidney disease:
* What kind of hereditary trend does the mutation have?
* What is the mutation in?
* What is the general epidemiolgy?
* Is it unilateral or bilateral?
* Adult PCK
* Autosomal dominant
* Mutation: PKD1 or PKD2 (less often) – both encode polycystin
* Membrane proteins that sense luminal flow
* Mutations result in dysregulation in tissue growth and cyst formation
* Epidemiology: common
* Always bilateral because hereditary
37
What disease is this?
* Childhood PCK
38
Name the diseases, but ignore B.
Summary
1. Multicystic dysplasia
2. Ignore this one
3. Autosomal dominant polycystic kidney disease
4. Autosomal recessive polycystic kidney disease
5. Nephronophthisis-medullary cystic disease complex
6. Medullary sponge kidney
39
How does acquired cystic disease occur and what does it put you at risk for?
What are simple cysts and what must you differentiate it from?
Acquired versus simple cysts
* Acquired cystic disease
* Develops after prolonged dialysis
* Increased risk of renal cell carcinoma
* Simple
* Single or multiple cortical cysts (benign)
* Must differentiate from renal cell carcinoma
40
What do the following give rise to:
* Intermediate mesenchyme?
* Lateral mesoderm?
* Paraxial mesoderm?
* The intermediate mesenchyme (mesoderm) produces the gonads and the kidneys
* The lateral mesoderm produces the heart and vasculature
* The paraxial mesoderm produces somites, which become muscles
41
How is the nephric duct created?
* Nephric duct (excretory duct)
* The rod lengthens from cranial to caudal to the cloaca
* It then proceeds to canalize (become hollow) from caudal to cranial
42
* What is the order of mesonephros, pronephros, and metanephros? How quickly do they degenerate and what is the function of each one?
* Pronephros
* First to develop and is superior
* Non-functional and immediately degenerates
* Mesonephros
* Develops inferior to and continuous with pronephros
* Briefly functions to produce urine until metanephros becomes kidneys
* Metanephros
* Primordium of the adult kidney
43
What are the two compoennts of the metanephros and how do they work?
* Ureteric bud (metanephric diverticulum)
* Elongates from the nephric duct and invades the metanephrogenic blastema
* Eventually produces the full kidney
* Metanephrogenic blastema (metanephric mesenchyme)
* Once connected to uretic bud, the blastemal cells undergo rapid differentiation to form ampulla
* Ampulla development initiates uretic bud to branch and divide to start the formation of nephrons
44
What is the process for the development of the nephron?
1. Mesenchymal cells cluster around the ampulla and develop lumens → forms vesicles
2. Vesicles then elongate to form and S-shaped tubule
1. One end of the tubule connects to the nephric duct
2. Other end of the tubule becomes Bowman’s capsule and surrounds the glomerulus
3. Collecting duct is formed from the uretic bud
4. Distal and proximal convoluted tubules form from mesenchymal cells
45
Do the kidneys move during development? If so, where and what would the diseases be as a result of a failure of this?
* Ascent of kidneys
* Normal: as body lengthens, kidneys move up to a new position in the abdomen from the pelvic area
* Abnormal:
* Renal artery variations
* Ectopic kidney
* **_Horseshoe kidney_**
46
For potter syndrome:
* What gender is usually affected?
* What are the two biggest effects and what can they cause?
* What is the appearance of the baby?
* Potter Syndrome
* Usually affects males
* Bilateral agenesis of kidneys – usually incompatible with life
* Oligohydraminos: insufficient amniotic fluid (made up of urine from fetus)
* Fetus is compressed (limb abnormalities; i.e. club feet)
* Pulmonary hypoplasia: cannot extract amino acids from amniotic fluid
* Stillborn of severe respiratory insufficiency after birth
* Facial appearance:
* Prominent fold and skin crease beneath each eye (Asian eyes)
* Blunted nose
* Depression between lower lip and chin
47
What two things does the urorectal septum cleave the cloaca into?
* Urorectal septum cleaves the cloaca into:
* Rectum
* Allantois (comes from umbilicus) is continuous with the urogenital sinus → bladder
48
What happens to the allantois post-partum and why does this occur?
* Post-partum: Allantois obliterates → urachus forms → medial umbilical ligament
* This is due to the fact that you no longer need an open canal from your umbilicus to your body
49
Label the B, C, and D urachal defects. What is another one that is not listed here?
* Anomalies of the urachus
* Patent urachus: open canal (A)
* Urachal cyst (B)
* Umbilical-urachus Sinus (C)
* Vesicourachal diverticulum (D)
50
How does the formation of the trigone occur?
* Formation of trigone
* The ureteric bud comes off of the mesonephric duct → becomes ureter
* Mesonephric duct becomes incorporated into the bladder wall to form the smooth trigone tissue structure
* In males, mesonephric ducts give way to the following: epididymis, vas deferens, and ejaculatory duct
51
What is the total kidney GFR and what is it NOT equal to?
* Total kidney GFR = sum of all the filtration rates in all functioning nephrons
* Index of functioning renal mass
* Urine produced does not equal GFR
52
For a substance to be used to measure GFR, what are some characteristics that it must meet? What are two examples?
* Characteristics suitable substance to measure GFR
* Freely filtered – not attached to protein
* Not reabsorbed
* Not secreted
* Not metabolized
* Examples: Inulin and Creatinine
* Creatinine is slightly secreted
53
What are the normal values of GFR? What is the equation used to measure GFR?
* Normal values: 90-120 ml/min
* Equation
* GFR = (Uinulin x V)/ Pinulin
* Ux – urine concentration of x
* V – volume of urine per hour
* Px – plasma concentration of x
54
How do you measure Fractional excretion?
* Fractional Excretion (FEx) = excreted/filtered = (Ux x V)/ (GFR x Px)
* FENA \< 1%; FENA \>\> 1%;
55
How do you measure filtered load and what is is measuring?
* Filtered Loadx = Px x GFR
* Amount filtered through glomerulus over time
56
Define renal clearance. What is the equation used? How does it tell you net secretion and net absorption?
* Renal Clearance
* Definition: Volume of plasma from which a substance is completely cleared by the kidneys per unit time
* Cinulin = GFR
* Cx = (Ux x V)/ Px
* Cx \> Cinulin - net secretion
* Cx \< Cinulin - net reabsorption
57
What are the advantages and distadvantages of using inulin?
* Inulin
* Advantages: gold standard
* Disadvantages: not used clinically because substance must be ingested by patient
58
For creatinine:
* What is its correlation to GFR?
* Advantages?
* Disadvantages?
* Creatinine
* Creatinine is inversely related to GFR
* Advantages: produced by the body’s muscles with relatively constant plasma concentration
* Disadvantage: secreted to a small extent, African American values are higher
59
What is the cockroft equation using serum creatnine to measure creatinine clearance?
* Ccreatinine = [weight x (140 -age)]/(72 x serum creatinine)
60
For BUN:
* What is the correlation to GFR?
* What is the biggest disadvantage?
* Blood Urea Nitrogen (BUN)
* BUN is inversely related to GFR
* Sensitive to changes in GFR
* Disadvantage: reabsorbed 40-50%, inaccurate indicator of kidney function during times of hypovolemia
* Urea reabsorption increased when NA and water reabsorption are increased
61
Crystalloids
small ions
62
Colloids
proteins and other large substances
63
Renal blood flow (RBF)
what fraction of CO is it?
* Renal blood flow (RBF) = 1.2 L/min
* ~ 20-25% cardiac output
64
Renal plasma flow (RPF)
Normal value? and what is it?
* Renal plasma flow (RPF) = 660 mL/min
* Plasma volume delivered to the kidneys (only filter plasma)
65
Filtration fraction (FF)
equation? normal value?
* Filtration fraction (FF) = volume filtered (GFR) / volume delivered (RPF)
* ~ 20%
66
Flow blood around nephron
* renal arteries à afferent arteriole à glomerular capillaries à efferent arterioles à peritubular capillaries à vasa recta à renal veins
67
What are the bloof supply's for bowman's capsule, PCT, DCT, and LH
* Bowman’s capsule – filtration (Cortex)
* Blood supply: glomerular capillaries
* 90% blood flow
* Proximal & Distal convoluted tubule – reabsorption (Cortex)
* Blood supply: peritubular capillaries
* 90% blood flow
* Loop of Henle – secretion/reabsorption (Medulla)
* Blood supply: vasa recta
* 10% blood flow
68
What are the two intrinsic ways renal blood flow are regulated?
Explain those two ways
* Autoregulation – RBF remains relatively constant between the pressures of 80-200 mmHg
* Myogenic
* Intrinsic property of smooth muscle – when stretched it distend on its own
* Tubuloglomerular feedback
* Macula densa – absorbs and senses increases in Na and Cl at JGA à releases paracrine vasoconstrictors à increased afferent arteriole constriction à decreased RBF
69
what are some extrinsic ways renal blood flow is regulated
* Nerves – Decreased BP à sympathetic nerves stimulation à renal vasoconstriction
* Hormones – RAAS
70
Explain in what ways these glomerulus filters?
what is it selective for?
exceptions?
* Basement membrane and podocytes contributes to size selectivity
* Endothelium contributes to positive charge selectivity
* Overall – prefers positive and small molecules
* Exception: small anions are unaffected by these filtration properties (i.e. Na and Cl have the same filterability)
71
Net Filtration Pressure (NFP)
* Net Filtration Pressure (NFP) = favoring filtration – opposing filtration
* = (PGC + pBS) - (PBS + pGC)
* pBS = 0, because no proteins can pass glomerulus
72
Glomerular Filtration Rate (GFR):
men versus women?
what is Kf
* Glomerular Filtration Rate (GFR): volume of fluid leaving the glomerular capillaries and entering into Bowman’s capsule per unit of time
* Higher in men
* GFR = Kf x NFP
* Filtration constant (Kf) = permeability x surface area
* Surface area is larger in glomerular capillary than in systemic capillaries, therefore higher Kf
73
Renal Vascular Resistance
where is the highest drop in resistance
* Highest pressure drop occur across the afferent and efferent arterioles because of highest site of vascular resistance
74
What are the parts of the JGA
what is it responsible for
* Juxtaglomerular Apparatus (JGA)
* 3 cell types
* Granular cells – synthesize renin
* Macula densa cells
* Extraglomerular mesangial cells
75
What is the main reabsorption and excretion going on at the DLH?
Reabsorbs water but not NaCl due to high osmolarity of medulla
76
What is the main reabsorption and excretion going on at the ALH (ARSH HAD PUT DLH HERE...WTF)?
including Na, K , Cl, Ca, Mg
This is very long... sorry?
* Reabsorbs NaCl, but not water (no aquaporins)
* NKCC2 (aka Na-K-Chloride-2) channel
* Dependent on Na, K-ATPase on basolateral membrane
* Located on luminal membrane
* Blocked by Lasix (furosemide) because it competes with Cl and NKCC2 channel requires all ions to be bound
* Cl- delivery is rate limiting
* Potassium channel (located on luminal membrane): K+ is recycled into the tubule
* Chloride channel (located on basolateral membrane): Cl- is reabsorbed into the peritubular capillary à creates a negative gradient
* Na+, Ca2+, Mg2+ are paracellularly transported across to the capillary due to the negative gradient
77
What is the main ion channels ar work at the DCT? what is going on?
filtrate come in at what osmorlatiy?
* At this point, the filtrate is hypo-osmotic as 90% NaCl and 80% water has been reabsorbed
* Na+, Cl- Symporter: located on the luminal membrane
* Blocked by thiazide diuretics by competing with chloride
78
What are the main channels that are play at the cortical collecting duct?
what are the two main cell types?
* Principal cells: contain Na+ (ENaC) and K+ channels on luminal membrane and Na+, K-ATPase on the basolateral membrane
* Can be horonally regulated by aldosterone
* Intercalated cells: contain a K+/H+ antiporter
79
What are the main channels at play at the medullary collecting duct?
whats the main hormone at play?
* ENaC Channels:
* Not aldosterone sensitive
* Water reabsorption proportional to ADH release
* Passive Cl- reabsorption
80
Explain regulation of plasma K+ and movement of K+ each part of nephron
is it reabsorbed or secreted at the PCT, ALH, CCD?
* Potassium is freely filtered and controlled within a small range
* Potassium is always moved against its concentration gradient due to its high intracellular fluid concentration
* Nephron Parts
* PCT
* Passive K+ reabsorption
* ALH
* K+ Reabsorbed
* Cortical Collecting Duct
* Principal: K+ secretion
* Intercalated: K+ reabsorption
81
What are the mechanisms of the aldosterone at the CCD?
* Aldosterone controls Na+ reabsoprtion in connecting segment and cortical collecting duct
* Aldosterone increases the number of Na+ channels (ENaC) [1] and increases Na+, K+ ATPase channels [2]
* Aldosterone (a corticosterioid) acts as a nuclear transcription factor for these channel proteins
* Aldosterone is regulated by circulated levels of Na+, K+, and Ang II
* Results in Na+ reabsorption, water retention, and potassium secretion
82
Liddle Syndrome
* Autosomonal dominant mutation in genes encoding ENaC
* Mechanism
* Decreased degradation of ENaC --\> Increased amount of channels --\> Increased Na+ reabsorption
* Mimics primary aldosteronism
* Tx: ENaC inhibitors, salt restriction, and renal transplant
83
explain urea reabsorption throughout the nephron
* Freely filtered
* At PT, water is reabsorbed therefore increases [urea] à urea is then reabsorbed passively and paracellularly
* At LH, urea is secreted
* At medullary collecting duct, urea is reabsorbed
84
Explain how BUN is useful as a lab value
what is azotemia?
* BUN
* Varies inversely with changes in GFR
* Exceptions:
* Increased urea production (i.e. high protein diet, glucocorticoids, trauma)
* Hypovolemia
* Increased BUN = azotemia
* Increased BUN, but no change in creatinine à volume depletion
* Increased BUN & creatinine à decreased GFR/renal function
85
how are organic cations excreted?
* Mediated by Organic Cation Transporters (OCT) in the PCT on the basolateral membrane
* Non-specific (activated by many cations) and driven by Na+, K+ ATPase
* Important for cation excretion
86
how are organic anions secreted?
* Organic Anions
* Mediated by Organic Anion Transporters (OAT) in mainly the PCT
* Requires energy
* Nonspecific (activated by many anions)
87
Paracellular
diffusion through tight junction in the lipid membrane
88
Transcellular
movement through apical (aka luminal) and basolateral membrane of a proximal tubular cell
89
Explain how Na is simply reabsorbed
* Na+/K+ ATPase reduces the concentration of Na+ in the tubular cell (inhibited by digoxin) creating a gradient
* Simple diffusion
* The reduced [Na+] allows Na+ to diffuse from the tubular lumen into the tubular cell via simple diffusion
90
What are two cotransport channels Na is involved in?
* Na+/H+ Antiport (NHE3)
* The reduced [Na+] allows Na+ to diffuse from the tubular lumen into tubular cell
* Water breaks down into H+ (participates in antiport and is excreted) and HCO3- (passes through basolateral mem brane)
* Symport
* The reduced [Na+] allows Na+ to diffuse from the tubular lumen into tubular cell and takes other substances like glucose down its gradient
91
Expliain how water is reabsorbed at the PCT?
* Water reabsorption – driven by Na+ concentration
* Aquaporins: proteins that allow for the diffusion of water across the membrane at faster rates than allowed with passive diffusion through lipid bilayer
92
Explain how Cl is reabsorbed at the PCT?
* Chlroide reabsorption
* Passive transport
* Occurs paracellularly due to chemical gradient created by active transport of Na+ and ultimately water
* Active transport
* Present, but not important
93
Describe the mechanism for glucose reabsorption
Difference for SGLT1 and SGLT2
which is a drug target? any related disease?
* Facilitated by Sodium-Glucose Transporter (SGLT)
* SGLT2 is located in the early PCT
* Low affinity/high capacity for glucose
* Autosomal recessive mutation in SGLT2 can cause familial renal glucosuria
* SGLT2 is often a drug target for Type II diabetes as it allows for glucose to be excreted rather than reabsorbed
* SGLT1 is located in the late PCT and intestine
* High affinity/low capacity for glucose
94
Explian this...
threshold, Tm, splay
* Normal: all glucose is reabsorbed in the PCT
* Transport maximum (Tm): maximal amount of material that can be reabsorbed per unit time
* Threshold: plasma concentration at which glucose _first_ appears in urine
* Splay: appearance of glucose in urine before Tm is reached because some nephrons may reach their individual Tm early stopping reabsorption
95
How is urine volume and osmolality related
what are average values
* Urine Volume and Osmolality
* Urine output is inversely related to urine osmolality
* i.e. more concentrated urine = less urine output and vice versa
* Average urine volume: 1 mL/min = 1.5 L/day
* Average urine osmolality: 500-800 mOsm/L
96
what is obligatory water loss?
* Obligatory water loss: volume of urine that must be excreted per day for the removal of waste products.
97
urine output per day
explain the difference between normal, sick and elderly patients for urine output per day
* Waste per day/Urinary concentration = Urine output per day
* Normal: (600 mOsm/day)/1200 mOsm/L) = 0.5 L/day
* Elderly: (600 mOsm/day)/600 mOsm/L) = 1.0 L/day
* Elderly cannot concentrate urine as well due to deteriorating kidneys
* Sick: (1200 mOsm/day)/1200 mOsm/L) = 1.0 L/day
* Sick patients have more waste products
98
Explain Concurrent Multiplier System
* Concurrent Multiplier System: production of concentrated urine
* Driven by the juxtamedullary nephrons to concentrate the urine via longer loops of Henle
* Dependent on different permeability and transport characteristics of DLH and ALH
* Steps
* Filtrate starts isosmotic à becomes hyperosmotic at the end of DLH à hyperosmotic filtrate forces salts and urea out of tubular lumen in ALH à generates a hyperosmotic medulla by absorbing salts
* When filtrate comes down the medullary collecting duct, the hyperosmotic medulla allows for the concentrating of the urine if water permeability is high (water into medulla down its gradient)
99
Explain Concurrent Exchange System
* Concurrent Exchange System
* Occurs in the vasa recta and protects the hyperosmotic medulla generated by the multiplier system
* Steps:
* In DLH, salts are reabsorbed into the vasa recta blood supply and water is excreted
* In ALH, salts are excreted out of vasa recta and water is reabsorbed
* This leaves slightly hyperosmotic blood (325)
100
Producing a concentrated urine
* ADH is high, therefore water permeability is high resulting in water reabsorption at the medullary collecting duct à urea is reabsorbed along with water
101
Producing a diluted urine
* ADH is low, therefore water permeability is low resulting in less water reabsorption at the medullary collecting duct à urea remains in the urine w/ H20
102
Urea - how does it relate to the gradient produced in the medulla
Makes up 50% of the osmotic gradient while salt makes up the other 50%
Protein-deficient patients cannot concentrate their urine because they are unable to generate the osmotic gradient necessary to reabsorb water
103
ADH
where is it secreted from?
mech?
Synthesis and secretion of ADH occurs in the hypothalamus
* Mechanism of Action of ADH in Distal Nephron
* ADH binds to V2 receptor à activates cascade à transcription factors bind DNA à creation of aquaporin proteins
104
Regulation of ADH (know first two for sure)
total: 6
* Systemic Blood pressure
* Via cardiac baroreceptors: Increased BP or increased volume decreased ADH secretion
* Plasma osmolality
* Via osmoreceptors in hypothalamus: Increased osmolality increases ADH secretion
* Angiotensin II: increases ADH
* Drugs/ETOH/Caffeine: decrease ADH (urination)
* Cold temperature: decreases ADH
* Vasoconstriction à blood is sent to the core à baroreceptors assume an increase in blood volume
* Sleep: increase in ADH
* Physiology unclear (possible decrease in BP)
105
Oliguria
2 causes?
* Oliguria can be caused by:
* Absolute decrease in GFR à renal dysfunction
* Retention of Na+ and water due to RAAS pathway or increased ADH
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Water diuresis
explain some causes and possible underlying disease
* Excessive intake
* Lack of ADH production
* As seen in central diabetes insipidus
* Lack of tubular response to ADH
* As seen in nephrogenic diabetes insipidus
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Osmotic diuresis
explain some causes and associated drug
* Excess solutes (i.e. glucose in DM patients)
* Inhibition of ion (Na+) reabsorption by drugs
* Mannitol (freely filtered)
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Carbonic Anhydrase (CA) Inhibitors
examples, pharmokinetics, MOA
* ![]()Prototypes: acetazolamide
* Pharmacokinetics: half-life is 13 hours
* MOA:
* Location: Proximal tubule
* Acts on carbonic anhydrase, indirectly affecting NHE3 (Na+/H antiporter)
* By inhibiting CA in the tubule, bicarbonate cannot turn into CO2 and H2O à decreases driving force of H+ across the luminal membrane
* Results in increased secretion of sodium, bicarb, potassium, and water
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Carbonic Anhydrase (CA) Inhibitors
AE, clinical use
* potassium, and water
* Side Effects:
* Metabolic acidosis
* Due to decreased H+ excretion/increased bicarb excretion
* K+ depletion
* Clinical
* Ineffective diuretics because rest of the nephron compensates
* Used in some cases of edema, glaucoma, and prophylactically in acute mountain sickness
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Loop Diuretics
examples, pharmokinetics, MOA
* Prototype: Furosemide (Lasix)
* Pharmacokinetics
* Rapid and short half life
* Highly protein bound; therefore less filtered
* For it to work, must be secreted by OATs
* MOA:
* Location: ALH
* Acts on the NKCC2 channel
* Competitively blocks Cl- à increased excretion of Na+, K+, Cl-, Mg2+, Ca2+ à loss of hyperosmotic medullary gradient
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Loop Diuretics
AE, clinical
* Side Effects
* Volume depletion, hypokalemia, MG2+ depletion, Hypochloremia
* Metabolic acidosis
* Transient drop in BP à Hypovolemia is sensed à aldosterone is increased à Na+ is reabsorbed and K+ is secreted à To compensate, K+ is reabsorbed in intercalated cells by secreting H+ ions (exchanger) à metabolic alkalosis
* Clinical
* Edema associated with cardiac, hepatic or renal disease
* Renal failure, HTN
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Thiazide Diuretics
examples, pharmokinetics, MOA
* Prototypes: hydrochlorothiazide (thiazides), chlorothalidone (thiazide-diuretics)
* Pharmacokinetics
* Orally administered and provides diuresis in 1 hour; wide range of half life
* MOA:
* Location: DCT
* Inhibits Na+/Cl- Symporter resulting in an increase in Na+, Cl-, K+, and water excretion
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Thiazide Diuretics
AE, clinical
* Side Effects:
* Hypokalemia metabolic alkalosis: similar to that of loop diuretics above
* Hyperuricemia: direct competition of thiazides for urate transport
* Hyperglycemia: diminished insulin secretion due to fall in serum K+
* Clinical
* Primary use: HTN
* Other uses: edema due to CHF, liver cirrhosis, hypercalciuria, and renal disease
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Spironolactone
MOA, clinical, AE
* MOA: Aldosterone antagonist
* Location: Principal cells of cortical collecting ducts
* Clinical: HTN, edema, HF, Primary hyperaldosteronism
* Side Effects: Hyperkalemia, androgen-like effects due to sterioid structure resulting in possible gynecomastia, GI disturbances
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Triamterene
MOA
* MOA: Na+ channel inhibitor
* Works as a blockade of apical Na+ channel (ENaC)
* Causes a drop in membrane potential, which is the driving force of K+ secretion
* Location: Principal cells of cortical collecting duct
116
Amiloride
MOA, clinical, AE
* MOA: blcoks Na/H+ exchanger
* Location: intercalated cells of cortical collecting duct
* Clinical: Edema, HTN
* Side Effects: hyperkalemia, metabolic acidosis (inhibits the Na/H exchange)
117
Differentiate between volatile and nonvolatile (“fixed”) acids’
how is each removed from body
* Volatile acids
* Acids produces from carbohydrate and fat metabolism (i.e. carbon dioxide à H2CO3)
* Removed by ventilation
* Nonvolatile acids
* Generated by protein/nucleic acid metabolism (i.e. sulfur containing amino acids à H2SO4)
* Removed by kidneys
118
Described 3 main physiological buffers and provide examples
* Buffer – any substance that reversibly consumes r releases H+
* Examples
* HCO3-
* CO2 + H2O ßà H2CO3 ßà H+ + HCO3-
* HPO42-
* NH3
* Hemoglobin and plasma protein
* Isohydric Principle: all buffers in the same system work together to control pH
119
Henderson-Hasselbalch equation
pH = pKa + log(base/acid)
120
what happens to bicarb for volatile and nonvolatile acids
* Freely filtered @ glomerulus
* For every HCO3- that is freely filtered, there is a HCO3- reabsorbed @ PCT
* Requires H+ for this to occur
* For every nonvolatile acid filtered through the glomerulus, there is a new HCO3- created and reabsorbed @ DCT
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what is the fate of H+ for volatile and nonvolatile acids
* H+ secretion prevents loss of HCO3-
* Filtered load HCO3- = PHCO3 x GFR = 4320 mEq/day
* This secreted H+ will be REABSORBED as HCO3- (1:1 ratio)
* H+ is actively secreted à combines with HCO3- à carbonic acid à carbonic anhydrase converts into CO2 and H2O à moves into the tubular cells à converted back into HCO3- à reabsorbed
* H+ secretion must also equal non-volatile acid production
* For every nonvolatile acid a secreted H+ will be EXCRETED (2nd picture)
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Describe the mechanism and importance of tubular production of NH4+
the difference between NH4 at PCT and CD
how is it different than the H+/HCO3- mechanism
* Importance: Body’s way of catabolizing glutamine and excreting the waste product as NH4
* MOA:
* ![]()PCT: Glutamine à into tubular cells from filtrate and blood à hydrolyzed into glutamate and NH4+ à metabolized into alpha-KG and NH4+ à
* CD: NH3 passively diffuses into tubular lumen and combines with H+ or NH4+ diffuses directly into lumen
* This mechanism can be upregulated to control for chronic acidosis unlike the previous mechanism of acid-base control
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Listed expected changes in A-B compensation in metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis
