Renal Flashcards
1
Q
What is the functional unit of the kidney?
A
Uriniferous tubule (nephron + collecting duct).
2
Q
What comprises the nephron?
A
Glomerulus (filters blood, makes ultrafiltrate) and tubular sustem (PCT, LOH, DCT) (filters ultrafiltrate, makes urine).
3
Q
What are the types of nephrons?
A
Cortical (6/7) and juxtamedullary (1/7).
4
Q
What is special about kidney circulation?
A
Has two capillary beds, an afferent arteriole -> CN (glomerulus) -> efferent arteriole -> CN -> venule. The second capillary network is either peritubular capillaries or vasa recta.
5
Q
What sort of tissue is the kidney primarily made of?
A
Epithelium.
6
Q
What tissue besides epithelium is in the kidney?
A
LCT renal intetstitium.
7
Q
What is the renal corpuscle?
A
The glomerulus and Bowman’s capsule. It has a vascular pole where the arterioles enter/leave, and a urinary pole where the PCT begins.
8
Q
Describe the Bowman’s space.
A
Has a parietal layer (simple squamous) and visceral layer (Podocytes).
9
Q
Describe the kidney filtration apparatus.
A
In the bowman’s space, the pore of the glomerular endothelial cell + the discontinuous basal lamina + the slit in the membrane between Pedicels. The filtration slits are covered in nephrin (hooked to an IC signalling pathway that communicates with the Podocyte).
10
Q
What are mesangial cells?
A
They are located between capillaries in the kidney - cover capillary surfaces not covered by podocytes. The extraglomerular ones are called lacis cells.
11
Q
What are the cells of the PCT and straight proximal tubule like?
A
Simple cuboidal - long, dense, apical microvilli. Boundaries between adjoining cells not clear or sharp. Many infoldings of BM and mitochondria to capacitate transporters, abundant pinocytotic pits and vesicles.
12
Q
Which cells secrete erythropoietin?
A
Fibroblasts in the PCT between the basement membrane of the tubule and the capillary.
13
Q
What are the cells of the thin Loop of Henle like?
A
Simple squamous.
14
Q
What are the cells of the ascending thick loop of Henle like?
A
Identical to distal tubule, simple cuboidal, no microvilli, lumen larger and ‘emptier’ than proximal tubule, has modified region called Macula Densa (taller).
15
Q
What comprises the juxtaglomerular apparatus?
A
The Macula Densa, Lacis cells, and Juxtaglomerular cells (in aferent arteriole, secrete renin).
16
Q
What does the macula densa do?
A
Senses sodium concentration in the urine (or lowered blood volume), and signals juxtaglomerular cells.
17
Q
What are the portions of the collecting duct?
A
Collecting tubule, cortical collecting duct, medullary collecting duct, papillary ducts/ducts of Bellini (end at renal papilla).
18
Q
What are the cells of the collecting duct like?
A
Simple cuboidal, distinct lateral boundaries. As the tube widens, the cells increase in height.
19
Q
What is the medullary ray?
A
Straight tubes (straight prox and distal tubules and also collecting duct) going to and from medulla.
20
Q
What things comprise the renal lobule?
A
The medullary ray and cortical labyrinth.
21
Q
What are the types of cells in the distal tubule and collecting duct?
A
Principal cells and intercalated cells (both cuboidal). Principal is more abundant, have numerous basal infoldings, distinct lateral margins, few microvilli. Intercalated cells are far fewer and actively secrete H+.
22
Q
What are primary cilia?
A
SOlitary projections found on almost all eukaryotic cells, immotile, act as antennae. In the kidney they are the primary sense for fluid flow coming out of the collecting tubule.
23
Q
What is Autosomal Dominant Polycystic Kidney Disease.
A
Primary cilia can no longer detect fluid dlow so the cell forms bigger tubules, eventually cysts form. Symptoms between 30-40 years of age.
24
Q
What is lined by urothelium?
A
Calyces, ureter, bladder, urethra.
25
What are the layers of the ureter?
Urothelium, basal lamina, muscularis mucosa, serosa (simple squamous epithelium).
26
What do glomerular capillaries do?
Only filtration.
27
What do peritubular capillaries do?
Absorption and secretion.
28
How much water and salts reabsorption is done in which parts of the kidney tubular system?
2/3 in proximal tubule, 1/3 in distal.
29
What is clearance?
The volume of plasma cleared of a substance per unit of time.
30
How is clearance calculated?
Urine flow X urine concentration / Arterial plasma (must make sure plasma concentration is constant) mL/min units.
31
What is filtration fraction? What is the normal?
GFR/RPF. 20%
32
What is fractional excretion?
Cx/GFR
33
What is normal renal blood flow?
1100mL/min (25% of CO)
34
What is normal RPF?
600mL/min.
35
How do you calculate the amount excreted?
Urine flow rate X urine concentration.
36
How do you calculate amount filtered?
GFR X Pa
37
What is special about inulin?
Ms = Mr = 0 C=GFR = 120mL/min
38
What is special about PAH?
Totally secreted - C=RPF = 600mL/min
39
What is special about glucose?
Totally reabsorbed, C=0 except for transport maximum.
40
What is a positive and negative N balance?
A net synthesis of body protein or a net breakdown
41
What are the purely glucogenic essential amino acids?
His, Met, Thr, Val.
42
What are the purely ketogenic essential amino acids?
Ile, Phe, Trp.
43
What are the essential amino acids that are both ketogenic and glucogenic?
Leu, Lys.
44
How is nitrogen carried back to the liver and kidney?
Via alanine and glutamine. Muscle preferably sends Ala, most peripheral tissues send Gln. Alanine goes straight to the liver, Glutamine can be broken to Alanine in the intestine, or the kidney can just use Glutamine for energy.
45
How are amino acids broken down?
First a nitrogen is transgered to an alpha-ketoglutarate by aminotransferase, making glutamate. The nitrogen can be released as ammonia by glutamate dehydrogenase (uses an NADP or an NADPH).
46
What is a common cofactor for aminotransferases?
B6.
47
When are AST and ALT elevated?
In liver disease. Also both are elevated in MI, muscle disorders. ALT is somewhat more specific for liver disease.
48
What does ALT do?
Transfers a nitrogen from Ala to alpha-ketoglutarate, making a glutamate.
49
What does AST do?
Transfers a nitrogen from Glu to oxaloacetate, making Aspartic Acid.
50
How does glutamate contribute to the urea cycle?
Converted to glutamine via glutamine synthetase in the tissues. Glutamine then goes to the liver and releases nitrogens via glutaminase to go to urea (regenerates glutamate).
51
What is the amino acid you want for the urea cycle?
Glutamate.
52
How does alanine contribute to the urea cycle?
In the liver amines are sent to glutamate (generating pyruvate).
53
How many grams of protein generate how much urea?
3g protein to 1g urea.
54
Describe the urea cycle.
Bicarbonate and ammonia converted to carbamoyl phosphate via carbamoyl phosphate synthetase I. Costs 2 ATPs. With ornithine and via ornithine transcarbamoylase, CP is made to citrulline. With aspartate and via arginosuccinate synthase, arginosuccinate is made. Costs 2ATPs. Via arginosuccinate lyase, fumarate and arginine are made. Arginine is then added to water and converted to ornithine and urea.
55
How is CPSI regulated?
N- acetylglutamate is an allosteric activator, arginine regulates its synthesis.
56
How are urea cycle deficiencies treated?
Avoid protein, fasting, low carbs, stress, replace amino acids with their alpha ketoacids. In the case of an arginosuccinate lyase deficiency, just give arginine (it can be excreted).
57
Where does the urea cycle take place?
In the mitochondria, but citrulline is sent to the cytosol.
58
How much energy does the urea cycle net use or make?
Makes 1 ATP.
59
What is the fate of fumarate?
Converted to malate, then oxaloacetate, then aspartate.
60
How can hyperammonemia be treated?
Benzoate (reacts with glycine to make hippuric acid), and phenybutyrate (converted to phenylacetate in body, reacts with glutamine).
61
In the filtration apparatus, what do the glomerulus capillary endothelium and the basement membrane do?
Capillary endothelium prevents cell penetration (pores 50-100nm), basement membrane prevents penetration of plasma proteins.
62
What sizes and charges of molecules are filtered better or worse?
under 18A are freely, \>42A not filtered. If between 18 and 42 then positively charged are filtered more and negatively charged are filtered less. If smaller than 18A, negatively charged are filtered more, positively charged are filtered less.
63
How do you calculate filtration rate/load of a freely filtered substance?
M = P x GFR
64
What is the Donnan Distribution?
r. Equal to the ultrafiltrate sodium concentration over hte plasma sodium concentration, or the plasma chlorine concentration over the ultrafiltrate chlorine concentration.
65
How do systemic capillaries allow for filtration and reabsorption?
Pc drops significantly along the capillary.
66
In glomerular capillaries, how is there such high filtraton?
Pc stays constant but pic increase (though never past Pc).
67
How does RPF affect GFR?
If it increases, GFR increases.
68
How does increased afferent arteriolar resistance affect GFR and RPF?
Decreases both. Decreased filtration.
69
How does increased efferent arteriolar resistance affect GFR and RPF?
Increases glomerular capillary pressure, increasing filtration but decreases RPF. So GFR effect unclear.
70
How does an increase in total resistance in kidney circulation affect filtration/reabsorption?
Increased reabsorption.
71
Describe myogenic kidney autoregulation.
Increased perfusion causes stretch in the smooth muscle, calcium enters via the stretch channels, influx causes constriction.
72
Describe tubuloglomerular feedback.
More fluid means more sodium coming in with the macula densa NCCK. This activates the Na+/K+ pump. More ATP is produced (and adenosine), binding to the P2X (and A1) receptor on smooth muscle calcium channel, causing vasoconstriction. Ca2+ also enters granular cells, decreasing renin release.
73
What triggers renin release?
Decreaed renal perfusion or hyponatremia.
74
What does renin do?
Activates angiotensinogen to angiotensin I. ACE converts ATI to ATII.
75
What does angiotensin II do?
A vasoconstrictor, causes release of aldosterone, causes thirst, causes release of ADH.
76
How is calcium reabsorbed in the kidney?
In the proximal tubule and the thick ascending loop of henle, there is an apical calcium channel, and a basolateral Ca++/3Na+ exchanger and a Ca++/2H+ ATPase.
77
What is reabsorbed in the first half of the proximal tubule?
Bicarbonate (lumen becomes more acidic), calcium, sodium, water, molecules (AAs, etc.)
78
What is reabsorbed and secreted in the second half of the proximal tubule?
Potassium (80%), NaCl, water, calcium reabsorbed. Anions secreted.
79
What is reabsorbed in the thick ascending loop of Henle?
Na+, Cl-, calcium.
80
Which part of the distal tubule is permeable to water?
Late.
81
What does the early distal tubule reabsorb and secrete?
Reabsorbs NaCl, can secrete potassium if necessary.
82
What do Principal cells reabsorb and secrete?
Reabsorb Na+, Cl- paracellularly. Can secrete potassium.
83
What do Intercalate cells reabsorb and secrete?
Reabsorb potassium (but can secrete) and chloride paracellularly. Secrete H+.
84
What is the effect of aldosterone?
Affects the late distal tubule and collecting duct. Increases expression of apical sodium channels, permeability of those channels, ATP synthesis, and the sodium/potassium pump. Increases potassium secretion and paracellular chloride reabsorption.
85
How does cortisol not cause aldosterone effects? They're similar compounds.
We have 11beta-hydroxysteroid dehydrogenase 2 which metabolizes cortisol. A deficiency may mimic mineralocorticoid excess.
86
How does licorice affect kidney metabolism?
It has glycyrrhetinic acid, which is an inhibitos of 11beta-HSD2.
87
How does potassium affect aldosterone?
Increased K+ concentration in plasma raises aldosterone.
88
What is the relationship between urine flow rate and potassium excretion?
Proportional.
89
Where can potassium be secreted?
DCT and CD.
90
How is H+ excreted in urine?
HPO4- filtered from the blood can react with some excreted H+ and make H2PO4 which is excreted 40mmol/day. Or inside the cell glutamine can release NH4+ which becomes NH3 and H+, which both leave and make NH4+ again ni the lumen (20-40mmol/day).
91
What is the effect of PTH on the kidney? What stimulates PTH release?
Increases calcium reabsorption, praticularly on the LOH and DCT. Increased plasma phosphate stimulates PTH release.
92
What is the effect of Vitamin D on salt absorption?
Increases calcium reabsorption in the kidney and interstitium, increases deposition of calcium in newly formed bone.
93
What is the effect of calcitonin on the kidney?
Inhibits calcium reabsorption in the LOH and DCT - increases calcium excretion.
94
What is the effect of calcitriol on the kidney?
Increases calcium reabsorption in the DCT.
95
How does reduction in ECV affect calcium reabsorption?
Increases it.
96
How does alkalosis affect potassium and calcium?
Increases calcium reabsorption, decreases potassium reabsorption.
97
How does acidosis affect potassium and calcium?
Decreases calcium reabsorption, increases potassium reabsorption.
98
What are some causes of hypokalemia?
Cell shifts, diarrhea, vomiting, direct renal loss (increased mineralocorticoid activity, increased distal sodium delivery), alkalosis.
99
What are some causes of hyperkalemia?
Cell shifts, direct renal retention (decreased mineralocorticoid activity, decreased distal sodium delivery), acidosis.
100
What are the cutoffs for hypo and hyperkalemia?
\<3.5 and \>5.0.
101
What is the effect of ADH on tubule fluid osmolarity?
Tubular fluid is hypoosmolar as it reaches the late distal tubule, if ADH is present water will be reabsorbed to equalize osmolarity.
102
What is the urine osmolarity by the end of the collecting duct?
Approaches the osmolarity of the IF in the deepest part of the medulla (~900-1100mosm/L).
103
How is urea processed in the kidney?
50% reabsorbed in proximal tubulr, 60% secreted in LOH (UT2), 70% reabsorbed in CD (UT1). ~40% excreted.
104
What is the urine osmolarity in the proximal tubule?
Isoosmolar to plasma.
105
What % of the GFR does ADH regulate?
20%.
106
What is the normal urine flow rate, and what is it at max diuresis and antidiuresis?
Normal = 1mL/min Max diuresis = 16mL/min Max antidiuresis = 0.3mL/min
107
How can water reabsorption be measured with inulin?
U/Pa
108
What is the maximum human urine concentrating ratio?
5X
109
How does ADH work?
It binds, stimulates a Gs mechanism, causes aquaporins to be moved to the luminal membrane.
110
How is ADH stimulated to be released.
Osmoreceptors (neurons) in the Nucleus Paraventricularis and Nucleus Supraopticus in the hypothalamus cause ADH to be released from the posterior pituitary (neurohypophysis). Baroreceptors also input to these neurons (low BP).
111
At what plasma osmolarity and blood volume is ADH releaed?
Plasma osmolarity \> 280, blood volume/pressure more than 10% reduced.
112
What is the relationship between urine excretion rate and urinosmolality?
Inverse.
113
What is diabetes insipidus?
ADH deficiency.
114
How is thirst and salt hunger regulated?
By the hypothalamus - osmolarity must increase by over 4mosm/L. Salt hunger also regulated by the hypothalamus, thirst developed immediately but salt hunger over hours or days.
115
What is Addison's disease?
When you can't make aldosterone.
116
How is arterial pressure related to urine volume?
Increased because blood flow from the vasa recta increases.
117
What are the natriuretic peptides? Where are they made?
ANP (atrium), BNP (kidney), urodilatin (CD), uroguanylin and guanylin (SI).
118
What do the natriuretic peptides do?
Dilate the afferent arteriole and constrict the efferent (increased GFR). Decreased aldosterone action, decreased sodium absorption, inhibition of water absorption by decreasing ADH action and release.
119
What are the renal effects of Angiotensin II?
Constricts both the afferent and efferent arterioles in the kidney. Decreases RBF, increases filtration fraction, increases peritubular osmotic pressure but decreases peritubular hydrostatic pressure. Increases sodium reabsorption in the proximal tubulr, decreases renal sodium and water excretion. Also decreases medullary blood flow (and so also washout), increasing medullary solutes. Lowers the set point of TGF. Promotes sodium reabsorption in the proximal tubule, thick aLOH, and early CT.
120
What can Serine be metabolized into?
3PG (from which it originates), pyruvate, Glycine.
121
What can Glycine be metabolized into and with what enzyme?
Oxalate, CO2 and NH3. Use of glycine cleavage enzyme.
122
What is non-ketotic hyperglycinemia? How do you treat it?
Lack of glycine cleavage enzyme. Give NMDA receptor blockers or Benzoic aid.
123
What can Threonine be metabolized into?
Pyruvate, Succinyl-CoA (via propionyl-CoA), can be made into Glycine and AcCoA.
124
What can Histidine be metabolized into?
Histidase can remove NH3 to make FIGlu, which can be converted to glutamate. FIGlu accumulates after an oral histidine load if there is a B9 deficiency.
125
What is histidemia?
AR histidase deficiency. No clinical phenotype.
126
How are branched chain amino acids metabolized?
Transaminated to alpha-ketoacids and then and then dealt with by branched chain alpha keto acid dehydrogenase. Val and Ile completion goes through propionylCoA, Leu goes through a purely ketogenic degradation.
127
What is MSUD?
Maple syrup urine disease, accumulation of branched chain amino acids and their alpha ketoacids.
128
Which amino acids go through propinoly CoA in their degradation?
Val, Ile, Met, Thr.
129
What is propionic acidemia? How do you treat it?
Deficiency of propionyl carboxylase (needs B9). Comes with recurrent metabolic acidosis, neurologic complications. Treat with dietary restriction.
130
What is methylmalonc acidemia? How do you treat it?
Deficiency of methylmalonyl CoA mutase (needs B12). Causes acidosis, ketosis in acute attacks. Treat with adenosyl-cobalamin or dietary protein restriction, avoidance of stress, avoidance of fasting and low-carb diets.
131
How is Methionine and Serine metabolized?
Serine is added to homocysteine and via cystathione synthase (B6), cystathione is made. Cystathione is degraded via cystathioninase into cysteine and alpha-ketobutyrate. alpha ketobutyrate made into propionyl-CoA, Cysteine made into pyruvate and sulfite is released.
132
What is homocystinuria? How do you treat it?
Deficiency of cystathione synthase (B6). Osteoporosis, ectopia lentis, thromboembolism (arterian and venous), mild mental deficiency, psychiatric problems. Give B6, maybe B9/B12, restrict methionine, give betaine to stimulate homocystine-to-methionine converstion.
133
What is cystathionuria?
A deficiency in cystathionase, no clinical symptoms. Cystathione accumulates.
134
How is Phenylalanine metabolized?
Made into Tyrosine via phenylalanine hydroxylase. Needs tetrahydrobiopterin and O2.
135
What is phenylketonuria? How do you treat it?
Autosomal recessive phenylalanine hydroxylase deficiency. Excess Phe causes mental retardation, light skin and hair, eczema, 'mousy' odor of infant. Tyrosine is now an essential amino acid. Treat by limiting Phe in diet, especially in pregnancy.
136
How is Tyrosine degraded/metabolized?
1) Transaminated to p-hydroxyphenyl pyruvate. 2) Turned into homogentisate via p-hydroxyphenyl pyruvate oxidase. 3) Turned into maleylacetoacetate via homogentisate oxidase. 4) Isomerized to fumarylacetoacetate. 5) Turned into fumarate and acetoacetate via fumarylacetoacetate hydrolase.
137
What important things is tyrosine involved in the synthesis of?
Melanin, catecholamines, serotonin.
138
What is alkaptinuria?
Deficiency of homogentisate oxidase. Homogentisate accumulates, black pigment deposits in cartilage, arthritis in elderly.
139
What is hepatorenal tyrosinemia? How do you treat it?
Deficiency of fumaryl acetoacetate hydrolase. Liver and kidney failyre, common in French Canadians. Treat with Phe/Tyr restriction, and inhibitor of p-hydroxyphenylpyruvate (NTBC).
140
What enzymes does a deficiency in biopterin metabolism affect?
Tyr, Trp, Phe hydroxylase.
141
What is hyperphenylalanemia?
A deficiency in any BH4 synthesis enzyme or in dihydropteridine reductase. Decreaed formation of catecholamines and serotonin.
142
Where is the macula densa?
Thick ascending loop of Henle.
143
What is the Henderson-Hasselbach equation?
pH=pKa + log [A-]/[HA]
144
What are the qualities of a good buffer?
pH and pKa difference less than 1.3, high concentration.
145
What is a phosphate buffer good for?
In ECF, bad in erythrocytes.
146
How is bicarbonate concentration affected by an increase of CO2 in and not in the presence of additional buffer?
An increase in CO2 barely affects the bicarbonate concentration, but having other buffers present will cause it to increase because it will reduce the H+.
147
What is the net H+ from metabolism that isn't balanced out by OH-?
80mmol.
148
How much H+ is excreted via the two methods of H+ excretion?
40mmol with each but ammonia can increase to as much as 500mmol.
149
What do you use to determine metabolic influence in acidosis and alkalosis?
Standard bicarbonate concentration (under 40mmHg and 37C), buffer bases/base excess (total concentration of all bases).
150
What is the normal plasma pH?
7.37-7.45.
151
What is a normal standard bicarbonate?
24
152
How is the venous blood relatively in respiratory acidosis compared to the arterial?
Increased PCO2, increased bicarbonate concentration, lowered pH.
