BECOM 2 Exam #3 Flashcards
(227 cards)
1
Q
renal blood flow
A
Renal artery -> segmental arteries -> interlobar arteries -> arcuate arteries -> interlobular arteries (aka cortical radiate arteries) -> afferent arterioles -> glomerulus -> efferent arterioles -> vein
2
Q
Podocytes and Pedicels
A
- are cells in the Bowman’s capsule in the kidneys that wrap around capillaries of the glomerulus
- star like projections off of the cell body
3
Q
Restrict Lamina densa Lamina rarae Fenestraiton Filtration Slits
A
Lamina densa: Restricts passage of larger proteins (middle)
lamina rarae: restricts passage of organic ions (internal and external)
Fenestration: RBCs and platelets
Filtration slits: small proteins, organic ions
4
Q
Mesangial cells
A
- Have contractile properties
- Provide support for capillaries
- Phagocytose mesangial matrix and protein aggregates that adhere to the filter
5
Q
PCT stain
A
Darker stain
Slightly larger cells
Occluded lumen
6
Q
DCT stain
A
Lighter stain
Smaller cells
Empty lumen
7
Q
Juxtaglomerular apparatus (JGA)
A
is a specialized sensory organ that helps to regulate blood flow through the glomerulus
8
Q
macula densa role
A
monitor the levels of ions in the lumen of the TAL
9
Q
Glomerulonephritis
A
Inflammation within the glomeruli
10
Q
ureteric bud makes up
A
ureter
renal pelvis
major/minor calyx
collecting duct
11
Q
metanerphric mesoderm makes up
A
Connecting tubule distal convoluted tubule loop of henle proximal convoluted tube renal (Bowman's) capsule renal glomerulus
12
Q
bladder is made from?
A
- upper portion of the urogenital sinus
- mesonephric ducts are incorporated into the posterior wall of the bladder to form the trigone of the bladder
13
Q
Renal agenesis vs Unilateral renal agenesis
A
- occurs when the ureteric bud fails to develop, thereby eliminating the induction of metanephric vesicles and nephron formation
- can be one kidney (assymptomatic) or both kidneys (still born)
14
Q
abnormal position (ectopic kidneys)
A
- Failure of the kidneys to ascend
- Pelvic kidneys are close to each other and usually fuse to form a discoid (“pancake”) kidney
15
Q
Renal fusion
A
- occurs when the inferior poles of the kidneys fuse across the midline
- A horseshoe kidney may also cause urinary tract obstruction due to impingement on the ureters:
- May lead to recurrent urinary tract infections
16
Q
Duplications of the urinary tract
A
ureteric bud divides abnormally or prematurely
17
Q
urachal cysts
A
- Remnants of the epithelial lining of the urachus form: urachal cysts
- Abnormal membranous sacs with fluid or semisolid material
18
Q
urachal sinus
A
- the patent inferior end of the urachus may dilate
- The lumen in the superior part of the urachus may also remain patent to form a urachal sinus that opens at the umbilicus
19
Q
urachal fistula
A
- Allows urine to escape from its umbilical orifice
- urine can seep from bladder to umbilicus
20
Q
Exstrophy of the bladder
A
is a deficiency of the anterior abdominal wall resulting from failure of mesoderm to migrate between the ectoderm and endoderm of the abdominal wall
21
Q
Epispadias
A
Urethra opens on dorsum of penis and wide separation of the pubic bones
22
Q
Supernumerary pelvic kidney
A
Results from the development of two ureteric buds
23
Q
Renal clearance equation
A
(U x V) / P
-MUST BE IN mL and mins
24
Q
Th1
A
-intracellular virus and bacteria
-Differentiating cytokine: IL-12
Release:
-INF-y: inc NK cells, inc macrophage phagolysosome, CSR -> IgG, inc INF-1 -> anti-viral state
-IL-2: activate CTLs
25
Th2
-allegens, parasites (helminth)
-Differentiating cytokine: IL-4
Release
-IL-4: CSR -> IgE
-IL-5: basophil and eosinophil recruitment/degranulation, mast cells
-IL-13: mucous production, anti-inflammation
26
Th17
-extracellular bacteria and fungi
-Differentiating cytokine: IL-23
Release:
-IL-17: inc neutrophil (via G-CSF, CLXL8, IL-8), inc antimicrobial peptide, release pro-inflammatory cytokines
-IL-22: wound healing
27
T reg
-absence of infection
-Differentiating cytokine: TFG-B
Release:
-TGF-B: FOXP3 expression in naive CD4+ cells
-IL-10: down regulate effector T cells, out compete CTLs and Th1 for IL-2, express CTLA-4
28
BTK
required for B cell development. Deficiency causes X-linked agammaglobulinemia (XLA).
29
CD21
bind to C3b opsonized antigen during cross linking
30
NKCC channel
- TAL symport Na+, K+ (or NH4+), Cl-, Cl-
- needs ROMK to work
- main transport of Na+ at TAL
31
ROMK channel
- TAL K+ secretion
- allows NKCC to work
- responsible for reabsorption of Mg+ because causes filtrate to become positive pushing Mg+ to blood via paracellular transport
32
Loop diuretics
inhibit NKCC
- Na+, K+, and Cl- loss
- can result in hypokalemia and hypocalcemia because no longer a positive gradient pushing positive ions via paracellular diffusion
33
NCC channel
- DCT1 Na+ and Cl- symport
- main Na+ transport in DCT1
- Thiazide diuretic-sensitive channel
34
BK channel
upregulated in the DCT2 and principal cell (CD) as a result of shear stress from increase flow rate
35
aldosterone effect at DCT
increases activity of ROMK, BK, NCC, ENaC, Na+-K+-ATPase (↑Na+ absorption, ↑K+ secretion)
36
upregulated ENac in collecting duct principal cells
```
Insulin
ADH/AVP
Catecholamines
↑Tubular fluid flow
Renal AngII
Aldosterone
```
37
upregulates ROMK in collecting duct principal cells
Aldosterone
| ↑dietary K+
38
Tubuloglomerular Feedback
- changes in systemic BP doesn't have a huge impact because of Tubuloglomerular Feedback and Myogenic autoregulation
1. high Na+ concentrations in DCT (means high GFR)
2. activation of macula densa cells that release ATP/ADP and activate extraglomerular mesangial cells via paracrine signaling
3. extraglomerular mesangial cells constrict the afferent capillary reducing GFR
39
Myogenic autoregulation
- changes in systemic BP doesn't have a huge impact because of Tubuloglomerular Feedback and Myogenic autoregulation
- Myogenic autoregulation: an increase of pressure on the renal capillaries causes smooth muscles to contract via membrane depolarization opens voltage-dependent Ca2+ channels
40
Congenital nephrotic syndrome cause of edema
Leakage of excessive protein into the GF. This results in a decrease of oncotic pressure in the systemic capillaries because of hypoproteinmia. H2O will leave the capillary to the interstitial fluid causing edema
-nephrin problem (holds pedicles together)
41
Net filtration pressure
glomerular capillary blood pressure – (plasma-colloid osmotic pressure + Bowman’s capsule hydrostatic pressure
42
Prostaglandin
- released when NaCl is low in DCT due to low Na+
- AA: dilated
- EA: dilated
- increases renal blood flow but no effect on GFR
- NSAIDs inhibit prostaglandin release
43
Atrial Neuritic Peptide
- released from heart when it has been stretched too far
- AA: dilate
- EA: constrict
- Inc GFR
44
Sympathetic stimulation
- AA: constrict
- EA: normal
- decrease GFR and renal blood flow but increase in Na+/H2O reabsorption
45
Angiotensin High and Low Levels
```
LOW
-AA: normal
-EA: constrict
-Inc GFR
HIGH
-AA: constrict
-EA: constrict
-Dec GFR
```
46
Filtration fraction and equation
Amount of plasma that gets filtered = 20% (normal)
FF = GFR / renal plasma flow
47
Filtration load and equation
The amount of substance that is filtered per time unit
Filtration load = GFR x Plasma conc
48
increases renin
1. reduced AA BP
2. Dec NaCl in DCTn (means hyponatremia (low Na+) inc renin -> inc Na+ reabsorption
3. inc sympathetic stimulation (via b1-adrenergic receptors)
49
Effects of Angiotensin II
1. Constricts arteriolar smooth muscle, causing mean arterial pressure to rise
2. Stimulates the reabsorption of Na+ via aldosterone
3. Release ADH from hypothalamus and activates the thirst center
4. Constricts efferent arterioles (DECREASES PERITUBULAR CAPILLARY HYDROSTATIC PRESSURE WHICH INCREASE FLUID REABSORPTION)
5. Causes glomerular mesangial cells to contract (dec surface area for filtration
50
ACEinh/ARB + diuretic + NSAID
- diuretic decreases BP
- normally anigiotensin will be released to keep GFR normal even with hypotension by constricting EA
- NSAIDs block prostaglandin and so no dilation of AA
51
NCB1
HCO3- and Na+ out of cell to blood
52
OAT1
alpha KG in exchange for PAH-
53
MRP
multidrug-related protein/ pump
| -PAH- to lumen with ATP
54
Removal of cations and anions (acidic and basic)
cation (+) removal: acidic (H+)
| anion (-) removal: basic (HCO3-)
55
Threshold concentration
plasma conc. At which a solute (e.g. glucose) will begin to appear in urine
56
transport maximum (Tm)
refers to the maximum amount of a given solute that can be transported per minute at the renal tubules
57
Calculation of Tm for solute reabsorption (Tr) (in mg/min) equation
(GFR or Cinu x Py) – (Uy x V)
58
RPF
UPAH x V ÷ (arterialPAH –venousPAH)
Cpah or ERPF / .9
-ERPF = CPAH
59
parathyroid hormone controls
Na+/phosphate uptake is under the control of PTH at the PCT (reduces the Tm for phosphate ions)
-Ca2+ reabsorption (vitamin D3)
60
Osmotic diuretics
- mannitol (I.V.) and glycerol (oral)
- increase the osmolarity of the filtrate keeping water in the filtrate and not allowing for a lot of reabsorption
- Useful in acute conditions such as cerebral edema and to reduce I.O. pressure in glaucoma
61
Thick ascending limb vs thin
The thin segment is permeable to water only, the thick is primarily permeable to salts
62
Tm secretion equation
(Uy x V) - (GFR or Cinu x Py)
63
loop diuretics (lasix)
- inhibit NKCC resulting in K+ and Na+ loss
- Thiazides downregulate TRPM6 causing hypomagnesemia
- Side effects: hypokalemia, hypocalcemia, hypomagnesia, increase urine bc increase filtrate solute
64
NKCC expression and phosphorylation is increased by
ADH
65
Change of osmolality along the nephron
PCT: isosmotic
Descending tubule: hyper osmotic (H20 reabsorbed)
TAL: hypotonic (Na+, Mg+, Ca2+ reabsorbed)
DCT: hyposmotic
66
loop diuretics causing hypertrophy
- loop diuretic inhibit Na+ reabsorption in the TAL
- this causes high levels of Na+ at the DCT1 which causes hypertrophy of the cells there and increase in NCC concluding in resistance to loop diuretics (thiazide)
67
ENaC filtration
-Influx of Na+ causes luminal fluid NEGATIVE -> increased paracellular absorption of Cl-
68
Aldosterone increases
- ENaCs (Na+ absorption) and ROMK (K+ secretion) trafficking and expression.
- aldosterone increases activity of ROMK, BK, NCC, ENaC, Na+-K+-ATPase (↑Na+ absorption, ↑K+ secretion)
- H+ ATPase and AE1
69
NCC is increased by
aldosterone, angiotensin II, insulin and ADH
70
PTH and vitamin D3 upregulate
TRPV5
71
TRPM6 stimulation
-STIMULATED BY EGF
72
up regulate ENaC
```
Insulin
ADH
Catecholamines
Tubular fluid flow
Renal AngII
```
73
Diabetes insipidus
is caused by the failure of the posterior pituitary gland to release vasopressin (ADH)
Gestational: placental vasopressinase break down mother's vasopressin
Central: lack of ADH or hypothalamic osmoreceptors
Nephrogenic: lack of functioning ADH receptors or AQP2
Amyloid degeneration, polycystic kidney
74
Syndrome of inappropriate ADH secretion (SIADH)
-continued secretion or action of ADH
-normal levels of Na+ but significant retention of H2O
Hyponatremia
Concentrated urine
Elevated urinary Na
-Individual that has hyponatremia give Na+ will drag H2O out of the neurons causing demyelination destroying the brain
75
AE1
-CD type A intercalated cell exchange HCO3- (in to blood) for Cl- (out of blood)
76
NDCBE and Pendrin
NDCBE: CD type 2 intercalated cell exchange Cl- (into lumen) for HCO3- and Na+
Pendrin: CD type 2 intercalated cell exchange HCO3- (into lumen) for Cl-
77
SN1 transporter
allows glutamine to enter cell from interstitial fluid during gluconeogensis
- at PCT
- increase during acidosis
78
Effect of acidosis on gluconeogenesis
↑ renal gluconeogenesis
↓ hepatic gluconeogenesis
↑ Glutamine basolateral transporters (SN1)
-uptake glutamine from blood into cell
In diabetic ketoacidosis ↑↑ renal gluconeogenesis
79
HPO4-2 Pka
6. 8
- H2PO4- in acidic environments
- HPO42- in basic environments
80
NH4+ Pka
9
81
NHE3
- exchanges Na+ (in) for H+ or NH3+ (out)
| - main Na+ reabsorbed at PCT
82
Rhcg/Rhbg
secrete NH3
83
Isosmotic dehydration
-Caused by hemorrhage, exudation of plasma from burned skin, GI fluid loss (vomiting, diarrhea)
84
Hyperosmotic dehydration
-Cases: Decreased intake, increased urinary loss (diabetes mellitus, diabetes insipidus, alcoholism, fever, excessive evaporation from skin .. Etc)
85
Isosmotic overhydration
-Caused by administration of large volume of isotonic NaCl and edema
86
Hyperosmotic overhydration
Cases: Oral or parentral intake of large amounts of hypertonic fluid
87
Hyposmotic overhydration
Excessive ingestion of water and inappropriate ADH secretion
88
The hypothalamic thirst center osmoreceptors are stimulated by and release
- ↑ Plasma osmolality of 2–3%
- Angiotensin II or baroreceptor input
- Dry mouth
- Substantial decrease in blood volume or pressure
-Release AVP (ADH)
89
Congestive heart failure and AVP production
During CHF the heart cannot pump blood effectively so the kidneys sees this as decrease blood volume. As a result there is an increase in AVP (ADH) production. This causes water retention and HYPONATREMIA -> edema
90
AVP signaling
1. AVP binds to V2 receptor on CD epithelial cell
2. activate G protein AC to make cAMP
3. cAMP -> inc PKA increase aquaporins in collecting duct
91
ADH stimulation causes
↑aquaporin-2 at connecting tubules, cotical CD and inner medullary CD
↑Na+K+ATPase at the distal nephron
↑NKCC and ROMK at the TAL
↑NCC at DCT1
↑ENaC at DCT2 and CD
↑ urea transporter (UT-A1) at the inner medulla
92
What all causes aldosterone release
angiotensin II
elevated K+ levels in the ECF
sympathetic stimulation
-slow effect (hours to days)
93
Estrogens
Increase NaCl reabsorption (like aldosterone) resulting in H2O retention during menstrual cycles and pregnancy
94
Progesterone
Decreases Na+ reabsorption (blocks aldosterone)
| -Promotes Na+ and H2O loss
95
Glucocorticoids
Increase Na+ reabsorption and promote edema
96
increases K+ uptake to the cells
insulin
| EPI
97
What influences Ca2+ reabsorption
- PTH (via TRPV5)
- Calcium reabsorption and phosphate excretion go hand in hand
- PTH inhibits phosphate reabsorption the PCT by decreasing the Tm
98
Low EABV
1. fire baroreceptors -> sympathetic stimulation -> inc renin via b1-adrenergic receptors
2. AA constriction ->
- less solutes filtered
- more efficient absorption
3. inc angiotensin II -> inc Na+/H2O absorption
99
hyperaldosterone
- hypernatremia (high Na+)
- hypervolemia -> hypertension
- hypokalemia
100
hypoaldosterone
- hyponatremia
- hypovolemia -> drop in BP
- hyperkalemia
101
FOXP3 mutation
APEX
102
ways to reduce risk of rejection
- ABO compatibility
- Match donor & recipient HLA as much as possible*
- Absence of anti-donor HLA antibodies in recipient (cross match)
- Post-transplant immunosuppressive treatment
103
Hyperacute rejection cause
preexisting antibodies against donor ABO or HLA class 1
104
Acute rejection cause
alloreactive T cells via direct or indirect allorecognition
105
Corticosteroids
-Inhibit inflammatory protein synthesis (NFκB)
Low doses predominantly affect APCs
High doses affect T cells
106
Cyclosporine and FK506 (Tacrolimus)
Inhibits calcineurin (Ca++ signaling) and NFAT, which impairs production of IL-2 (T cell growth factor)
107
Rapamycin
Inhibits mTOR and T cell proliferation
108
IL-2 blockade (Basiliximab)
Inhibits IL-2 signaling and T cell proliferation
109
Graft Versus Host Disease
when a Hematopoietic Stem Cell Transplantation (HSCT) is conducted mature T cells that are in donor bone marrow attack recipient tissue
110
G-CSF
M-CSF
GM-CSF
neutrophils
macrophages
dendritic cells
111
Immunosuppressive meds B cell infections vs T cell infections
B cell: encapsulated organisms
| T cell: virus and fungi
112
chronic
alloreactive T cell via indirect recognition
113
Complement-dependent cell cytotoxicity (CDCC)
classical pathway of complement is activated by IgM (best) or IgG (IgG3 & IgG1>>>IgG2, not IgG4). Complement cascade terminates with the membrane attack complex (MAC), which perforates (& kills) target
114
Antibody-dependent cell cytotoxicity (ADCC)
activating receptors on NK cells include FcRγIII. When NK cells bind IgG Fcr via FcRγIII, NK cells induce apoptosis of target cell (perforin & granzyme).
115
Clonal deletion
multivalent antigen -> strong BCR cross-linking
| -mediated centrally and peripherally by Fas/FasL
116
Receptor editing
requires continued RAG expression and continued rearrangement of light chain V-J segments. Receptor editing is UNIQUE to B cells
117
Anergy
- low valence, soluble antigen; unresponsive to signaling, Anergic B cells cannot be activated by their cognate antigen even with T cell help.
- B cell becomes activated by binding with protein but doesn't get Th help -> anergy
- T cell recognizes antigen presented on an MHC molecule without costimulation
118
BTK
is required for B cell development. Deficiency causes X-linked agammaglobulinemia (XLA)
119
Agammaglobulinemia
is a group of inherited immune deficiencies characterized by a low concentration of antibodies in the blood due to the lack of particular lymphocytes in the blood and lymph
120
Subcapsular macrophages and follicular dendritic cells
-low endocytic activity, so they display whole, unprocessed antigen
121
required for naive B cell recognition
CD21 (C3d-opsonized pathogen (antigen) will induce cross-linking of co-Rc (CD21 complex))
CD19
CD81
Igalpha and Igbeta
122
dark zone
- proliferation/blasting/ clonal expansion (“centroblasts”)
| - SHM and CSR
123
light zone
- antigen capture and linked recognition (“centrocytes”)
| - B cell test affinity with FDCs then bind with Tfh -> recognition initiates clonal expansion again
124
Memory B cells
-100X increased frequency over naïve B cells specific for same antigen
-BCR with increased affinity
-Populate lymph nodes, spleen, circulation
Are first antibody-secreting (plasma) cells at onset of secondary response
125
Memory T cells
- 100-1000X increased frequency over naïve T cells specific for same antigen
- Effector memory T cells localize to tissues & respond rapidly to re-stimulation
- Central memory T cells remain in lymphoid tissues & are slower & less effective effectors upon re-stimulation—likely have greater role in maintaining memory pool
126
Long-lived plasma cells
- Antibody with increased affinity
| - Predominantly populate bone marrow
127
Hyper IgM cause
frequently caused by (X-linked) mutations in CD40L, CD40 and AID
128
Selective IgA deficiency
-is the most common PID
129
Berger’s disease
IgA nephritis where IgA gets lodges in the glomerulus
| -Excess monomeric IgA w/defective galactosylation
130
Hyper IgE syndrome
-is caused by (AD or AR) mutations in txn factors important for Th17 polarization, resulting in aberrant Th2 differentiation. Abundant IL-4 -> IgE
131
Wiskott-Aldrich
- syndrome is caused by (X-linked) mutations in WASp
| - Decreased IgM, normal IgG, elevated IgA/IgE, and T cell defects
132
immune-privileged tissues
central nervous system, the eye, and parts of the reproductive systems
- hard for T cells and Ig to cross barrier to enter
- Fas/FasL expressed that induces apoptosis in T cells that gain entry
133
Activation-induced cell death (AICD)
occurs in T cells that have been exposed repeatedly to the same antigen via Fas/FasL
134
Fas/FasL
- FasL expressed predominantly in activated T & NK cells
- FasL triggers death of cells expressing Fas
- Fas and FasL are both found on the CTL and when two cells get close together Fas binds to FasL and apoptosis occurs to cell presenting Fas
135
autoimmune lymphoproliferative syndrome (ALPS)
-lack of Fas/FasL
136
Foxp3+ deg
IPEX—Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked
137
Tregs
- express high affinity IL-2R that allow them to out compete effector T cells for IL-2
- can bind to MHC II molecules that posses self antigens and harmless environmental antigens
- inhibit neighboring T cells by secreting the cytokines interleukin 10 (IL-10) or TGF-β
138
natural Tregs (Tregs)
in the thymus can be produced if a thymocyte recognizes self antigen plus MHC class II at high affinity producing the trans factor FOXP3
139
Induced Tregs (iTregs)
naive CD4+ cells that are exposed to TGF-B in the periphery
140
If an immature B cell is producing antibody in response to antigen in the gut in the presence of TGF-β, it will class switch to immunoglobulin
IgA
141
CTLA-4
- expressed by activated T cells and has a higher affinity for B7 than CD28
- Regulates proliferation & effector responses to limit immune-mediated pathology
142
CTLA-4 def
autoimmune lymphoproliferative syndrome (ALPS).
143
PD-1
- PD-1 is unregulated on T cell when there is persistent activation
- PD-1 will bind to PD-1L on normal/abnormal cell inhibiting T cell function
- PD-1 blockers bind to either PD-1 or PD-1L blocking contraction allowing T cells effector function to persist
144
Atopy
an immediate hypersensitivity reaction to environmental antigens mediated by IgE
145
Allergic March
individuals develop different types of allergy throughout their lives
146
Allergens
antigens which trigger allergic reactions
147
peanut allergen
ARA h2 early in life, ARA h8 later in life
148
Cardiac hypertrophy is caused by
increased BP via catacholemines and angiotensin II which result in an increase of
- calcineurin ->NFAT
- CaMKII -> MEF-2
- IL-6 -> Jak/STAT pathway
149
Physiologic hypertrophy pathway
- PKB-P -> Akt -> uTOR -> UEBP -> CIF4E -> proliferation
- activation of uTOR inhibits UEBP which inhibits CIF4E
- inhibition of an inhibitor allows CIF4E (phosphorylated) to be turn on
150
glucocorticoids
myostatin
NF-kappaB
glucocorticoids: class of corticosteroid important for muscle protein degradation
myostatin: inhibitor of muscle fiber growth
NF-kappaB: key signaling hub and transcription factor
151
cause of hyperplasia
loss of APC
152
Barrett’s esophagus
metaplasia
Gastroesophogeal junction:
-chronic acid reflex causes stomach cells to migrate to esophagus
153
Mechanisms of cell injury
- ATP depletion: dec Ox Phos -> dec ATP -> inc glycolysis, dec protein production, Na+/K+ ATPase disruption
- mitochondrial damage: inc cytosolic Ca2+, inc ROS, lipid peroxidase
- entry of Ca2+
- membrane damage
- protein misfolding, DNA damage
154
Reperfusion restores blood flow to ischemic tissues and can promote recovery, but can also exacerbate injury. HOW?
ROS “burst” upon reperfusion (either due to damaged mitochondria or damaged antioxidant defense mechanisms); intracellular calcium overload; inflammatory response elicited by neutrophil recruitment/influx + activation of complement system
155
Proteotoxic stress
- build up of misfolded protein due to lack of chaperones
| - results in inc chaperone, dec protein synthesis, and inc protein degradation
156
Players of type I hypersensitivity
```
Antigen (Allergen)
APC
TH2 cell
B cell
IL-4
Plasma Cells
IgE
FceR1 receptor (high affinity)
Mast Cell (or Eosinophil)
Inflammatory molecules
```
157
Serum Sickness Vasculitis
- receive a passive immunization containing animal Ig
- upon second treatment Type III hypersensitivity reaction can occur that attacks animal Ig
- diphtheria, tetanus, and gangrene
158
issues with plasma creatine and GFR
- age and muscle can determine change levels
- must have a large change in GFR for creatinine levels to change
- secreted
159
ACE-inhibitors diuretics
```
Reduce angiotensin II
Reduce blood pressure
INCREASE GLOMERULAR FILTRATION
Increase K+ retention and Na+ loss (loss of aldosterone production)
Reduce ADH secretion
```
160
infected in medulla of kidney
- no blood flow to the medulla resulting in glomerular filtration and reabsorption of solutes at the PCT and DCT but no blood flow to the loop of henle and collecting duct where H2O is absorbed
- result: increase in dilute urine
161
IL-8
neutrophil recruitment
162
AVP is released in response to
Suppression
Increased plasma Osmolarity
Drop in plasma volume (effective arterial blood volume/EABV)
Angiotensin II
Thirst
Emotional stress
Pain, trauma, anesthetics, morphine, nicotine
Suppression: ANP and alcohol
163
Why do we make more urine when swimming in colder water?
Bc vasoconstriction inc the effective plasma volume causing water to go into urine to reduce volume
164
change in AVP mainly because
osmolarity more than volume
165
Increase in arterial blood pressure leads to
increased urine output (pressure diuresis)
166
Locally at the kidneys low EABV will
- inc renin by action of stretch receptors at AA
- dec net filtration pressure
- dec peritubular hydrostatic pressure and speed increase the renal reabsorption
167
where does gluconeogenesis occurs in the kidneys
cortex
168
main source for renal gluconeogenesis
lactate > glycerol > glutamine > alanine
169
Hormonal regulation of renal glucose release
```
insulin:
-increase glucose uptake
-increase lactate and glycerol uptake for glycolysis
epinephrine:
-increase glucose release
-gluconeogenesis
```
170
Ammonia transport at PCT
-NH3 diffusion to lumen
-NH4+ transport via NHE3 (exchange Na+ to cell for NH4+ to lumen)
Substituting NH4+ for K+
171
Ammonia transport at TAL
- NH4+ uses NKCC2
| - Basolateral NHE4 (mutation causes ↑↑ ammonia in urine) exchanges Na+ (in) for NH4+ (to blood)
172
Ammonia transport at CD
Rhbg: excrete NH4+ (on base lateral side only)
Rhcg: excretes NH4+ (on basolateral and lumenal side)
173
Effect of acidosis on ammoniagenesis
↑ glutamine transporters (SN1)
↑ glutamate dehydrogenase/GDH (yields NH4+)
↑ phosphoenolpyruvate carboxykinase/PEPCK (eliminate the reverse reaction)
↑ NHE3 at PCT
↑ NKCC2 at TAL
↑Rhcg expression and apical translocation
174
Metabolism of glutamine
2 x NH4+ and 2 x HCO3-
- in ACIDOSIS there is an increase of glutamine uptake
- PCT is the primary cite for production of NH3/NH4+
175
Tumor lysis syndrome
necrosis of large volume of cells causing
- hyperuricemia
- hyperkalemia
- hyperphosphatemia
- hypocalcemia
176
AST and ALT
shows hepatocrit necrosis
177
Net acid excretion =
urinary titratable acid + urinary ammonia – urinary HCO3- (usually not applicable)
178
man absorption of HCO3-?
PCT
179
Decreased blood pH causes
```
↑ NHE3 activity
↑ H+-ATPase
↑ renal ammonia synthesis and secretion
↑ glutamine transporters
↑ glutamate dehydrogenase/GDH (yields NH4+)
↑ PEPCK
↑ NKCC2 at TAL
↑Rhcg expression and apical translocation
```
180
Hypertension effect on blood pH
- decreases NHE3 so there is more Na+ secretion
| - results in increase H+ in blood -> acidosis
181
Na+ effect on blood pH
- decrease NHE3 -> H+ accumulation in blood
- increase ENaC
- filtrate more negative -> blood becomes alkalotic
- more K+ secreted -> hypokalemic -> metabolic alkolosis
182
diabetes mellitus
so much glucose in the blood that it is excreted and the huge filtration load retains water in the lumen
183
effect on vasopressin (ADH)
- recognized by hypothalamus osmoreceptors -> released from posterior pituitary
- decreased vascular pressure also stimulates vasopressin release but
- angiotensin increases release
- osmolarity has a greater effect than volume
- alcohol inhibit vasopressin release -> inc urine
184
vasopressin vs aldosterone (speed)
vasopressin: fast bc peptide
aldosterone: slow bc steriod
185
UT-A1 and A3
urea transporter at the inner medulla
| -inc with ADH
186
increase BP effect on pH
- metabolic acidosis bc decreases NHE3 activity causing retention of H+
- less ENaC activity -> filtrate not as negative so less of a gradient for H+ to move to filtrate
187
inhibition of CAII
- decrease blood pH
| - dec HCO3-
188
aldosterone effect on pH
- decreases pH
- stimulate H+ATPase
- stimulate ENaC which makes filtrate more negative favoring H+ secretion
- promotes K+ secretion via ROMK causing hypokalemia -> cellular K+ to blood and H+ into cell -> alkalosis
189
IL-4
CSR to IgE
190
IL-5
basophil eosoniphil mast cell recruitment and degranulation
191
IL-13
mucous production and anti inflammatory
192
Exstrophy of the bladder
- failure of mesoderm to migrate between the ectoderm and endoderm of the abdominal wall
- Exposure and protrusion of the mucosal surface of the posterior wall of the bladder
193
Pathologic hypertrophy molecules
NFAT
MEF-2
Jak/STAT
194
DNA damage mechanism
ATM -> CHK2 and P53
| ATR -> CHK1 -> P53
195
intrinsic vs extrinsic apoptosis
intrinsic: 8 -> 3
extrinsic: 9 -> 3
196
amiloride
inhibits ENaC
197
NCX1
Na+ into cell and Ca2+ to blood at DCT
198
ENac at DCT2 vs ENaC at principal cells stimulation
DCT2: ADH and aldosterone
principal: ang II, aldosterone, ADH, estrogen, insulin, catecholamine, high tubular flow
199
autoimmune hemolytic anemia
antibodies bind and destroy RBC
-extravascular: FcR phagocytosis
-intravascular: compliment MAC complex
TYPE II cytotoxic
200
Good pasture syndrome
IgG induces ADCC to the basement membrane of the lungs and kidney
TYPE II cytotoxic
201
Grave's disease
IgG binds to TSH receptor causing continual release of T4
-proptosis
TYPE II non cytotoxic
202
Myasthenuia Gravis
antibody binds to Ach receptor inhibiting neuromuscular signaling
-Ptosis, diplopia
TYPE II non cytotoxic
203
Lupus Nephritis (SLE
antinuclear antibodies bind to self antigen (DNA, RNA) -> released during UV damage and immune complexes get lodges in the basement membrane of the glomerulus
-"Butterfly” rash, photosensitivity
Type III (SYSTEMIC)
204
Type 1 Diabetes Mellitus (T1DM)
generally CTLs attack insulin secreting pancreatic B cells then diffused damage effect pancreatic islet cells
-antibodies against pancreatic islet cell
-Polydipsia (extreme thirst), polyphagia (extreme hunger)
-MHCII
TYPE IV
205
Hashimoto’s Disease
mediated destruction of the thyroid
-Autoantibodies against thyroglobulin & thyroid peroxidase
TYPE IV
206
Addison’s Disease
destruction of the adrenal cortex
-Elevated ACTH & low cortisol & aldosterone -> hypotension
-Autoantibodies against 21-hydroxylase
TYPE IV
207
Multiple Sclerosis
destruction of myelin
| TYPE IV
208
Crohn’s Disease
inflammatory response to microbiom in the ileum and other parts of the GI tract
TYPE IV
209
Celiac Disease
gliadin is broken down by transglutaminase to form gliadin peptides which has antibodies against it
TYPE IV
210
Ankylosing Spodylitis
inflammation of the intervertebral joints of the lower back
| TYPE II-IV (SYSTEMIC)
211
Rheumatoid Arthritis
chronic inflammation of joints
-Citrullinated Proteins (autoantigen
TYPE II-IV (SYSTEMIC)
212
Phase I reaction
| Phase II reaction
Phase I reaction: chemicals undergo hydrolysis, oxidation, or reduction
-most important phase I enzyme P-450 enzyme
Phase II reaction: conjugation reactions include glucuronidation, sulfation, methylation
213
ozone danger
low ozone causes NO and O- (free radical) that damages epithelial cells of the resp tract
214
lead
- binds to sulfhydryl groups in proteins
- inhibits enzymes of heme synthesis, δ-aminolevulinic acid dehydratase and ferrochelatase (microcytic hypochromic anemia)
- competes with calcium
215
Mercury
- binds to sulfhydryl groups in proteins leading to damage in the CNS and kidney
- depletes glutathione
216
Arsenic
- interference with mitochondrial oxidative phosphorylation by replacing phosphates in adenosine triphosphate
- dark pigments on hands
217
Cadmium
- Toxic to kidneys and lungs
- obstructive lung disease due to necrosis of alveolar epithelial cells, and renal tubular damage
- uptake into cells via transporters (ZIP8, normally a transporter for zinc)
218
Effects of tobacco
- increased elastase production and injury, emphysema
| - polycyclic hydrocarbons and nitrosamines are potent carcinogens
219
Effects of alcohol
Ethanol -> acetaldehyde -> acetic acid
- alcohol dehydrogenase then aldehyde dehydrogenase
- break down requires NAD and depletes NAD leading to accumulation of fat in the liver and metabolic acidosis
- NAD is required for fatty acid oxidation in the liver and for the conversion of lactate into pyruvate
- accumulation of fat in the liver
220
Two drugs that most frequently caused adverse reactions
- oral anticoagulants warfarin and dabigatran
| - Main complications associated with both are bleeding, maintaining anticoagulation
221
Acetaminophen
- metabolized through CYP2E to NAPQI
- NAPQI is normally conjugated with glutathione (GSH), but with large dosages of acetaminophen, glutathione becomes depleted and unconjugated NAPQI accumulates and causes liver cell injury and necrosis that may progress to liver failure
222
cocaine
inhibits dopamine reuptake
| -May induce myocardial ischemia and precipitate lethal arrhythmias
223
opiates
distinctive right-sided tricuspid valve endocarditis caused by S. aureus
-Right side bc venous return
224
Superficial burns
Partial thickness burns
Full-thickness burns
Superficial burns (formerly first-degree burns) are confined to the epidermis
Partial thickness burns (formerly second-degree burns) involve injury to the dermis
Full-thickness burns (formerly third-degree burns) extend to the subcutaneous tissue
225
With >20% of body surface burns
```
a rapid (within hours) shift of body fluids into the interstitial compartments
-Pseudomonas aeruginosa
```
226
Hyperthermia
Heat cramps: result from loss of electrolytes via sweating
Heat exhaustion: heavy sweating leading to hypovolemia
Heat stroke: no sweat
227
ionizing radiation
- direct damage or indirect via formation of ROS that damage DNA
- Vascular changes and interstitial fibrosis
