BECOM 2 Exam #3 Flashcards
renal blood flow
Renal artery -> segmental arteries -> interlobar arteries -> arcuate arteries -> interlobular arteries (aka cortical radiate arteries) -> afferent arterioles -> glomerulus -> efferent arterioles -> vein
Podocytes and Pedicels
- 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
Restrict Lamina densa Lamina rarae Fenestraiton Filtration Slits
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
Mesangial cells
- Have contractile properties
- Provide support for capillaries
- Phagocytose mesangial matrix and protein aggregates that adhere to the filter
PCT stain
Darker stain
Slightly larger cells
Occluded lumen
DCT stain
Lighter stain
Smaller cells
Empty lumen
Juxtaglomerular apparatus (JGA)
is a specialized sensory organ that helps to regulate blood flow through the glomerulus
macula densa role
monitor the levels of ions in the lumen of the TAL
Glomerulonephritis
Inflammation within the glomeruli
ureteric bud makes up
ureter
renal pelvis
major/minor calyx
collecting duct
metanerphric mesoderm makes up
Connecting tubule distal convoluted tubule loop of henle proximal convoluted tube renal (Bowman's) capsule renal glomerulus
bladder is made from?
- upper portion of the urogenital sinus
- mesonephric ducts are incorporated into the posterior wall of the bladder to form the trigone of the bladder
Renal agenesis vs Unilateral renal agenesis
- 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)
abnormal position (ectopic kidneys)
- Failure of the kidneys to ascend
- Pelvic kidneys are close to each other and usually fuse to form a discoid (“pancake”) kidney
Renal fusion
- 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
Duplications of the urinary tract
ureteric bud divides abnormally or prematurely
urachal cysts
- Remnants of the epithelial lining of the urachus form: urachal cysts
- Abnormal membranous sacs with fluid or semisolid material
urachal sinus
- 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
urachal fistula
- Allows urine to escape from its umbilical orifice
- urine can seep from bladder to umbilicus
Exstrophy of the bladder
is a deficiency of the anterior abdominal wall resulting from failure of mesoderm to migrate between the ectoderm and endoderm of the abdominal wall
Epispadias
Urethra opens on dorsum of penis and wide separation of the pubic bones
Supernumerary pelvic kidney
Results from the development of two ureteric buds
Renal clearance equation
(U x V) / P
-MUST BE IN mL and mins
Th1
-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
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
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
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
BTK
required for B cell development. Deficiency causes X-linked agammaglobulinemia (XLA).
CD21
bind to C3b opsonized antigen during cross linking
NKCC channel
- TAL symport Na+, K+ (or NH4+), Cl-, Cl-
- needs ROMK to work
- main transport of Na+ at TAL
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
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
NCC channel
- DCT1 Na+ and Cl- symport
- main Na+ transport in DCT1
- Thiazide diuretic-sensitive channel
BK channel
upregulated in the DCT2 and principal cell (CD) as a result of shear stress from increase flow rate
aldosterone effect at DCT
increases activity of ROMK, BK, NCC, ENaC, Na+-K+-ATPase (↑Na+ absorption, ↑K+ secretion)
upregulated ENac in collecting duct principal cells
Insulin ADH/AVP Catecholamines ↑Tubular fluid flow Renal AngII Aldosterone
upregulates ROMK in collecting duct principal cells
Aldosterone
↑dietary K+
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
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
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)
Net filtration pressure
glomerular capillary blood pressure – (plasma-colloid osmotic pressure + Bowman’s capsule hydrostatic pressure
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
Atrial Neuritic Peptide
- released from heart when it has been stretched too far
- AA: dilate
- EA: constrict
- Inc GFR
Sympathetic stimulation
- AA: constrict
- EA: normal
- decrease GFR and renal blood flow but increase in Na+/H2O reabsorption
Angiotensin High and Low Levels
LOW -AA: normal -EA: constrict -Inc GFR HIGH -AA: constrict -EA: constrict -Dec GFR
Filtration fraction and equation
Amount of plasma that gets filtered = 20% (normal)
FF = GFR / renal plasma flow
Filtration load and equation
The amount of substance that is filtered per time unit
Filtration load = GFR x Plasma conc
increases renin
- reduced AA BP
- Dec NaCl in DCTn (means hyponatremia (low Na+) inc renin -> inc Na+ reabsorption
- inc sympathetic stimulation (via b1-adrenergic receptors)
Effects of Angiotensin II
- Constricts arteriolar smooth muscle, causing mean arterial pressure to rise
- Stimulates the reabsorption of Na+ via aldosterone
- Release ADH from hypothalamus and activates the thirst center
- Constricts efferent arterioles (DECREASES PERITUBULAR CAPILLARY HYDROSTATIC PRESSURE WHICH INCREASE FLUID REABSORPTION)
- Causes glomerular mesangial cells to contract (dec surface area for filtration
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
NCB1
HCO3- and Na+ out of cell to blood
OAT1
alpha KG in exchange for PAH-
MRP
multidrug-related protein/ pump
-PAH- to lumen with ATP
Removal of cations and anions (acidic and basic)
cation (+) removal: acidic (H+)
anion (-) removal: basic (HCO3-)
Threshold concentration
plasma conc. At which a solute (e.g. glucose) will begin to appear in urine
transport maximum (Tm)
refers to the maximum amount of a given solute that can be transported per minute at the renal tubules
Calculation of Tm for solute reabsorption (Tr) (in mg/min) equation
(GFR or Cinu x Py) – (Uy x V)
RPF
UPAH x V ÷ (arterialPAH –venousPAH)
Cpah or ERPF / .9
-ERPF = CPAH
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)
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
Thick ascending limb vs thin
The thin segment is permeable to water only, the thick is primarily permeable to salts
Tm secretion equation
(Uy x V) - (GFR or Cinu x Py)
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
NKCC expression and phosphorylation is increased by
ADH
Change of osmolality along the nephron
PCT: isosmotic
Descending tubule: hyper osmotic (H20 reabsorbed)
TAL: hypotonic (Na+, Mg+, Ca2+ reabsorbed)
DCT: hyposmotic
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)
ENaC filtration
-Influx of Na+ causes luminal fluid NEGATIVE -> increased paracellular absorption of Cl-
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
NCC is increased by
aldosterone, angiotensin II, insulin and ADH
PTH and vitamin D3 upregulate
TRPV5
TRPM6 stimulation
-STIMULATED BY EGF
up regulate ENaC
Insulin ADH Catecholamines Tubular fluid flow Renal AngII
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
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
AE1
-CD type A intercalated cell exchange HCO3- (in to blood) for Cl- (out of blood)
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-
SN1 transporter
allows glutamine to enter cell from interstitial fluid during gluconeogensis
- at PCT
- increase during acidosis
Effect of acidosis on gluconeogenesis
↑ renal gluconeogenesis
↓ hepatic gluconeogenesis
↑ Glutamine basolateral transporters (SN1)
-uptake glutamine from blood into cell
In diabetic ketoacidosis ↑↑ renal gluconeogenesis
HPO4-2 Pka
- 8
- H2PO4- in acidic environments
- HPO42- in basic environments
NH4+ Pka
9
NHE3
- exchanges Na+ (in) for H+ or NH3+ (out)
- main Na+ reabsorbed at PCT
Rhcg/Rhbg
secrete NH3
Isosmotic dehydration
-Caused by hemorrhage, exudation of plasma from burned skin, GI fluid loss (vomiting, diarrhea)
Hyperosmotic dehydration
-Cases: Decreased intake, increased urinary loss (diabetes mellitus, diabetes insipidus, alcoholism, fever, excessive evaporation from skin .. Etc)
Isosmotic overhydration
-Caused by administration of large volume of isotonic NaCl and edema
Hyperosmotic overhydration
Cases: Oral or parentral intake of large amounts of hypertonic fluid
Hyposmotic overhydration
Excessive ingestion of water and inappropriate ADH secretion
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)
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
AVP signaling
- AVP binds to V2 receptor on CD epithelial cell
- activate G protein AC to make cAMP
- cAMP -> inc PKA increase aquaporins in collecting duct
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
What all causes aldosterone release
angiotensin II
elevated K+ levels in the ECF
sympathetic stimulation
-slow effect (hours to days)
Estrogens
Increase NaCl reabsorption (like aldosterone) resulting in H2O retention during menstrual cycles and pregnancy
Progesterone
Decreases Na+ reabsorption (blocks aldosterone)
-Promotes Na+ and H2O loss
Glucocorticoids
Increase Na+ reabsorption and promote edema
increases K+ uptake to the cells
insulin
EPI
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
Low EABV
- fire baroreceptors -> sympathetic stimulation -> inc renin via b1-adrenergic receptors
- AA constriction ->
- less solutes filtered
- more efficient absorption
- inc angiotensin II -> inc Na+/H2O absorption
hyperaldosterone
- hypernatremia (high Na+)
- hypervolemia -> hypertension
- hypokalemia
hypoaldosterone
- hyponatremia
- hypovolemia -> drop in BP
- hyperkalemia
FOXP3 mutation
APEX
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
Hyperacute rejection cause
preexisting antibodies against donor ABO or HLA class 1
Acute rejection cause
alloreactive T cells via direct or indirect allorecognition
Corticosteroids
-Inhibit inflammatory protein synthesis (NFκB)
Low doses predominantly affect APCs
High doses affect T cells
Cyclosporine and FK506 (Tacrolimus)
Inhibits calcineurin (Ca++ signaling) and NFAT, which impairs production of IL-2 (T cell growth factor)
Rapamycin
Inhibits mTOR and T cell proliferation
IL-2 blockade (Basiliximab)
Inhibits IL-2 signaling and T cell proliferation
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
G-CSF
M-CSF
GM-CSF
neutrophils
macrophages
dendritic cells
Immunosuppressive meds B cell infections vs T cell infections
B cell: encapsulated organisms
T cell: virus and fungi
chronic
alloreactive T cell via indirect recognition
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
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).
Clonal deletion
multivalent antigen -> strong BCR cross-linking
-mediated centrally and peripherally by Fas/FasL
Receptor editing
requires continued RAG expression and continued rearrangement of light chain V-J segments. Receptor editing is UNIQUE to B cells
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
BTK
is required for B cell development. Deficiency causes X-linked agammaglobulinemia (XLA)
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
Subcapsular macrophages and follicular dendritic cells
-low endocytic activity, so they display whole, unprocessed antigen
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
dark zone
- proliferation/blasting/ clonal expansion (“centroblasts”)
- SHM and CSR
light zone
- antigen capture and linked recognition (“centrocytes”)
- B cell test affinity with FDCs then bind with Tfh -> recognition initiates clonal expansion again
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
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
Long-lived plasma cells
- Antibody with increased affinity
- Predominantly populate bone marrow
Hyper IgM cause
frequently caused by (X-linked) mutations in CD40L, CD40 and AID
Selective IgA deficiency
-is the most common PID
Berger’s disease
IgA nephritis where IgA gets lodges in the glomerulus
-Excess monomeric IgA w/defective galactosylation
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
Wiskott-Aldrich
- syndrome is caused by (X-linked) mutations in WASp
- Decreased IgM, normal IgG, elevated IgA/IgE, and T cell defects
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
Activation-induced cell death (AICD)
occurs in T cells that have been exposed repeatedly to the same antigen via Fas/FasL
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
autoimmune lymphoproliferative syndrome (ALPS)
-lack of Fas/FasL
Foxp3+ deg
IPEX—Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked
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
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
Induced Tregs (iTregs)
naive CD4+ cells that are exposed to TGF-B in the periphery
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
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
CTLA-4 def
autoimmune lymphoproliferative syndrome (ALPS).
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
Atopy
an immediate hypersensitivity reaction to environmental antigens mediated by IgE
Allergic March
individuals develop different types of allergy throughout their lives
Allergens
antigens which trigger allergic reactions
peanut allergen
ARA h2 early in life, ARA h8 later in life
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
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
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
cause of hyperplasia
loss of APC
Barrett’s esophagus
metaplasia
Gastroesophogeal junction:
-chronic acid reflex causes stomach cells to migrate to esophagus
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
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
Proteotoxic stress
- build up of misfolded protein due to lack of chaperones
- results in inc chaperone, dec protein synthesis, and inc protein degradation
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
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
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
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
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
IL-8
neutrophil recruitment
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
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
change in AVP mainly because
osmolarity more than volume
Increase in arterial blood pressure leads to
increased urine output (pressure diuresis)
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
where does gluconeogenesis occurs in the kidneys
cortex
main source for renal gluconeogenesis
lactate > glycerol > glutamine > alanine
Hormonal regulation of renal glucose release
insulin: -increase glucose uptake -increase lactate and glycerol uptake for glycolysis epinephrine: -increase glucose release -gluconeogenesis
Ammonia transport at PCT
-NH3 diffusion to lumen
-NH4+ transport via NHE3 (exchange Na+ to cell for NH4+ to lumen)
Substituting NH4+ for K+
Ammonia transport at TAL
- NH4+ uses NKCC2
- Basolateral NHE4 (mutation causes ↑↑ ammonia in urine) exchanges Na+ (in) for NH4+ (to blood)
Ammonia transport at CD
Rhbg: excrete NH4+ (on base lateral side only)
Rhcg: excretes NH4+ (on basolateral and lumenal side)
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
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+
Tumor lysis syndrome
necrosis of large volume of cells causing
- hyperuricemia
- hyperkalemia
- hyperphosphatemia
- hypocalcemia
AST and ALT
shows hepatocrit necrosis
Net acid excretion =
urinary titratable acid + urinary ammonia – urinary HCO3- (usually not applicable)
man absorption of HCO3-?
PCT
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
Hypertension effect on blood pH
- decreases NHE3 so there is more Na+ secretion
- results in increase H+ in blood -> acidosis
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
diabetes mellitus
so much glucose in the blood that it is excreted and the huge filtration load retains water in the lumen
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
vasopressin vs aldosterone (speed)
vasopressin: fast bc peptide
aldosterone: slow bc steriod
UT-A1 and A3
urea transporter at the inner medulla
-inc with ADH
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
inhibition of CAII
- decrease blood pH
- dec HCO3-
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
IL-4
CSR to IgE
IL-5
basophil eosoniphil mast cell recruitment and degranulation
IL-13
mucous production and anti inflammatory
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
Pathologic hypertrophy molecules
NFAT
MEF-2
Jak/STAT
DNA damage mechanism
ATM -> CHK2 and P53
ATR -> CHK1 -> P53
intrinsic vs extrinsic apoptosis
intrinsic: 8 -> 3
extrinsic: 9 -> 3
amiloride
inhibits ENaC
NCX1
Na+ into cell and Ca2+ to blood at DCT
ENac at DCT2 vs ENaC at principal cells stimulation
DCT2: ADH and aldosterone
principal: ang II, aldosterone, ADH, estrogen, insulin, catecholamine, high tubular flow
autoimmune hemolytic anemia
antibodies bind and destroy RBC
-extravascular: FcR phagocytosis
-intravascular: compliment MAC complex
TYPE II cytotoxic
Good pasture syndrome
IgG induces ADCC to the basement membrane of the lungs and kidney
TYPE II cytotoxic
Grave’s disease
IgG binds to TSH receptor causing continual release of T4
-proptosis
TYPE II non cytotoxic
Myasthenuia Gravis
antibody binds to Ach receptor inhibiting neuromuscular signaling
-Ptosis, diplopia
TYPE II non cytotoxic
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)
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
Hashimoto’s Disease
mediated destruction of the thyroid
-Autoantibodies against thyroglobulin & thyroid peroxidase
TYPE IV
Addison’s Disease
destruction of the adrenal cortex
-Elevated ACTH & low cortisol & aldosterone -> hypotension
-Autoantibodies against 21-hydroxylase
TYPE IV
Multiple Sclerosis
destruction of myelin
TYPE IV
Crohn’s Disease
inflammatory response to microbiom in the ileum and other parts of the GI tract
TYPE IV
Celiac Disease
gliadin is broken down by transglutaminase to form gliadin peptides which has antibodies against it
TYPE IV
Ankylosing Spodylitis
inflammation of the intervertebral joints of the lower back
TYPE II-IV (SYSTEMIC)
Rheumatoid Arthritis
chronic inflammation of joints
-Citrullinated Proteins (autoantigen
TYPE II-IV (SYSTEMIC)
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
ozone danger
low ozone causes NO and O- (free radical) that damages epithelial cells of the resp tract
lead
- binds to sulfhydryl groups in proteins
- inhibits enzymes of heme synthesis, δ-aminolevulinic acid dehydratase and ferrochelatase (microcytic hypochromic anemia)
- competes with calcium
Mercury
- binds to sulfhydryl groups in proteins leading to damage in the CNS and kidney
- depletes glutathione
Arsenic
- interference with mitochondrial oxidative phosphorylation by replacing phosphates in adenosine triphosphate
- dark pigments on hands
Cadmium
- Toxic to kidneys and lungs
- obstructive lung disease due to necrosis of alveolar epithelial cells,andrenal tubular damage
- uptake into cells via transporters (ZIP8, normally a transporter for zinc)
Effects of tobacco
- increased elastase production and injury,emphysema
- polycyclic hydrocarbons and nitrosamines are potent carcinogens
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
Two drugs that most frequently caused adverse reactions
- oral anticoagulants warfarin and dabigatran
- Main complications associated with both are bleeding, maintaining anticoagulation
Acetaminophen
- metabolized through CYP2E to NAPQI
- NAPQI is normally conjugated with glutathione (GSH), but with large dosages of acetaminophen, glutathione becomes depleted and unconjugatedNAPQIaccumulates and causes liver cell injury andnecrosisthat may progress toliver failure
cocaine
inhibits dopamine reuptake
-May inducemyocardial ischemiaand precipitatelethal arrhythmias
opiates
distinctive right-sided tricuspid valve endocarditis caused byS. aureus
-Right side bc venous return
Superficial burns
Partial thickness burns
Full-thickness burns
Superficial burns(formerly first-degree burns) are confined to the epidermis
Partial thickness burns(formerlysecond-degree burns) involve injury to the dermis
Full-thickness burns(formerlythird-degree burns) extend to the subcutaneous tissue
With >20% of body surface burns
a rapid (within hours) shift of body fluids into the interstitial compartments -Pseudomonas aeruginosa
Hyperthermia
Heat cramps: result from loss of electrolytes via sweating
Heat exhaustion: heavy sweating leading to hypovolemia
Heat stroke: no sweat
ionizing radiation
- direct damage or indirect via formation of ROS that damage DNA
- Vascular changes and interstitial fibrosis
