First Aid Flashcards
1
Q
Fomepizole
A
Inhibits alcohol dehydrogenase - antidote for methanol or ethylene glycol intoxication
2
Q
Disulfiram
A
Inhibits acetaldehyde dehydrogenase - DIScourages drinking
3
Q
Occur in mitochondria + cytoplasm
A
Heme synthesis, urea cycle, gluconeogenesis (HUG’s take 2)
4
Q
Rate determiner - glycolysis
A
phosphofructokinase-1
Activated by - AMP, fructose-2,6,biphosphate
Inhibited by - ATP, citrate
5
Q
Rate determiner - gluconeogenesis
A
Fructose-1,6-biphosphate
Activated by - citrate
Inhibited by - AMP, fructose-2,6-biphosphate
6
Q
Rate determiner - TCA cycle
A
Isocitrate dehydrogenase
Activated by - ADP
Inhibited by - ATP, NADH
7
Q
Rate determiner - glycogenolysis
A
Glycogen phosphorylase
Activated by - epinephrine, glucagon, AMP
Inhibited by - glucose-6-phosphate, insulin, ATP
8
Q
Rate determiner - HMP shunt
A
G6PD
Activated by - NADP+
Inhibited by - NADPH
9
Q
Rate determiner - de novo pyrimidine synthesis
A
Carbamoyl phosphate synthetase II
Activated by - ATP, PRPP
Inhibited by - UTP
10
Q
Rate determiner - de novo purine synthesis
A
PRPP - glutamine phosoribosylpyrophosphate amidotransferase
Inhibited by - AMP, IMP, GMP
11
Q
Rate determiner - urea cycle
A
Carbamoyl phosphate synthetase I
Activated by - n-acetylglutamate
12
Q
Rate determiner - Fatty acid synthesis
A
Acetyl-CoA carboxylase
Activated by - insulin, citrate
Inhibited by - glucagon, palmitoyl-CoA
13
Q
Rate determiner - Fatty acid oxidation
A
Carnitine acyltransferase
Inhibited by malonyl CoA
14
Q
Rate determiner - Ketogenesis
A
HMG CoA synthase
15
Q
Rate determiner - Cholesterol synthesis
A
HMG coA reductase
Activated by - insulin, thyroxine
Inhibited by - glucagon, cholesterol
16
Q
Rate determiner - glycogenesis
A
Glycogen synthase
Activated by - glucose-6-phosphate, insulin, cortisol
Inhibited by - epinephrine, glucagon
17
Q
Galactokinase
A
Mild galactosemia
18
Q
galactose-1-phosphate uridyltransferase
A
Severe galactosemia
19
Q
Hexokinase/glucokinase
A
Glucose –> Glucose-6-phosphate
Hexokinase - most tissues except liver - low Km (high affinity) - low Vmax low capacity - Feedback inhibited
Glucokinase - liver and beta-cells of pancreas - high Km (low affinity) - high Vmax high capacity no feedback inhibition by glucose-6-phosphate
20
Q
Glucose-6-phosphatase
A
Von Gierke disease
21
Q
Glucose-6-phosphate dehydrogenase
A
Necessary for glucose-6-phophate–> 6-phosphgluconolactone in HMP shunt
Transketolase: ribulose-5-phosphate –> fructose-6-phosphate (leaves HMP shunt) - thiamine cofactor
22
Q
Phosphofructokinase-1
A
Conversion of F-6-P –> F-1,6-biphosphate
Rate limiting step in glycolysis
Activated by - AMP, fructose 2,6,-biphosphate
Inhibited by - ATP, citrate
23
Q
fructose 1,6 biphosphatase
A
Conversion of F-6-P
24
Q
Fructokinase
A
Essential fructosuria - benign
25
Aldolase B
Fructose intolerance - NOT benign
hypoglycemia, jaundice, vomitting, cirrhosis.
26
Pyruvate kinase
PEP --> pyruvate - irreversible
27
Pyruvate dehydrogenase
pyruvate --> acetyl CoA - irreversible - thiamine cofactor
28
HMG-CoA reductase
HMG-CoA --> mevalonate --> cholesterol
29
Pyruvate corboxylase
Pyruvate --> oxaloacetate - Biotin cofactor
30
PEP carboxykinase
Oxaloacetate --> PEP
31
Isocitrate dehydrogenase
Isocitrate --> alpha-ketoglutarate
32
alpha-ketoglutarate dehydrogenase
alpha-ketoglutarate --> succinyl CoA - requires Thiamine
33
Ornithine transcarbomylase
Ornithine --> citrulline - Urea cycle
34
Propionyl-CoA Carboxylase
Propionyl CoA --> mehtylmalonyl CoA - biotin cofactor
35
Arsenic
Glycolysis nets 0 ATP
36
NAD+ vs. NADPH
NAD+ - catabolic
NADPH - anabolic processes - product of HMP shunt
37
Pyruvate dehydrogenase complex deficiency
Causes buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT)
Findings: Neuro defects, lactic acidosis, increased serum alanine
treatment: increase intake of ketogenic nutrients
38
Electron transport inhibitors
Rotenone - complex one
An-3-mycin - antimycin - complex 3
Cyanide, CO, and azide - complex 4`
39
Oligomycin
ATP synthase inhibitor - no ATP produced
40
Fructokinase deficiency
Essential fructosuria - benign
41
Aldolase B deficiency
Fructose intolerance - BAD
Fructose-1-phosphate accumulates and uses available phosphate
Hypoglycemia, guanidine, cirrhosis, vomitting
Treat by decreasing fructose and sucrose in diet
42
Galacokinase deficiency
Benign - galactilol accumulates
galactosemia, galactosemia, and infantile cataracts.
May appear as inability to track objects and develop social smile.
43
Galactose-1-phosphate uridyltransferase deficiency
BAD
Galctilol accumulates
FTT, jaundice, hepatomegaly, infantile cataracts, intellectual disability. E. Coli sepsis in neonates
Treat by decreasing lactose and galactose in diet.
44
Aldose reductase
transforms glucose --> sorbitol to trap it in cell.
Sorbitol dehydrogenase converts Sorbitol --> fructose
Lack of this enzyme --> intracellular sorbitol accumulation causes osmotic damage - cataracts, retinopathy, and peripheral neuropathy seen in hyperglycemia.
45
Essential amino acids
PVT TIM HALL
| Phenylalanine, valine, tyrosine, threonine, isoleucine, met, His, leucine, lysine
46
Glucogenic AA's
Met, his, val - I MET HIS VALentine, she is so sweet
47
Gluco/ketogenic
Isoleucine, she, threonine, tyrosine
48
Ketogenic
Leucine, lysine
49
Basic AA's
Arg, his, lys - HIS LYS Ar basic
(+) charge at physiologic pH
Arrginine is most basic
Arg+his required for growth
Arg+lysine are increased in histones with bind negatively charged DNA.
50
Acidic AA's
glutamic acid, and aspartic acid
(-) charge at physiologic pH
51
Hyperammonemia
Excess. NH3 depletes GABA in the CNS and alpha-ketoglutarate --> Inhibition of the TCA cycle
Treatment - limit protein
To decrease ammonia levels:
- lactulose 0 acidify GI tracts and trap NH4+
- Abx to decrease colonic ammoniagenic bacteria
- Benzoate, phenylacetate, or pheylbutarate - react w/ glycine or glutamine --> form really excreted products.
52
Ornithine transcrabamylase deficiency
x-linked recessive
Interferes w/ bodies ability to eliminate ammonia.
Excess carbamoyl phosphate is converted to orotic acid (increased levels in blood and urine)
Decreased BUN and symptoms of hypoerammonemia.
53
Phenylalanine derivative
Tyrosine --> thyroxine OR DOPA
DOPA --> Melanin or dopamin
Dopamine --> NE (Vit. C co-factor)
NE --> Epi (SAM)
54
Tryptophan
- -> Niacin --> NAD+/NADP+
| - -> Seratonin --> melatonin
55
Glycine
--> porphyrin --> heme
56
Glutamate
- -> GABA
| - -> Glutathione
57
Arginine
- -> Creatinine
- -> Urea
- -> NO
58
Phenylketonuria
decreased BH4 or phenylalanine hydroxylase
Tyrosine is essential
Decrease phenylalanine and increase tyrosine in diet, supplement BH4 - avoid aspartame
59
MSUD
Blocked degradation of branched chain Das (leucine, isoleucine, valine) d/t decreased branched chain alpha-ketoacid dehydrogenase.
Increased alpha-ketoacids in blood
CNS defects, intellectual disability, death. Presents w/ vomitting, poor feeding
Treatment: restrict branched chain AA's, supplement w/ thiamine
60
Alkoptanuria
Homogentisate oxidase deficiency --> pigment forming homogentisic acid accumulates in tissue
AR - Usually benign
Findings: Blue/black CT (ear cartilage and sclerae), urine black on air exposure. May have debilitating arthralgias
61
Homocysteinuria
Ostoperosis, marfanoid habitue, ocular changes (lens subluxation down and in), cardiovascular (thrombosis/athersclerosis), kyphosis, intellectual disability.
Causes:
- Crystathione synthase deficiency: Decrease met in diet, increase cysteine, B6, B12, and folate.
- Decreased affinity of crystathione synthase for pyridoxal phosphate: treat with B6 and cysteine in diet
- Methionine synthase deficiency: increase Met in diet
62
Cystinuria
Defect of renal PCT and intestinal AA transporter that prevents reabsorption or Cysine, Ornithine, Lysine, and Arginine (COLA)
Recurrent precipitation of hexagonal cystine stones
Tx: hydration, urine alkalinization, chelating agents.
63
Periodic acid schiff stain
identifies glycogen
64
Von Gierke
Type I glycogen storage disease - glucose-6- phosphatase deficiency
Severe fasting hypoglycemia, increased glycogen in liver and kidneys, increased blood lactate, increased triglycerides, increased rica acid, hepatomegaly, renomegaly.
Tx: Frequent oral glucose
Impaired glycogenolysis and gluconeogenesis
65
Pompe
Type II glycogen storage disease - lysosomal acid alpha-1,4-glucosidase with alpha-1,6-glucosidase activity deficiency
POMPE trashes the pump (heart, liver, muscle)
Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, hypotonia. Early death.
66
Cori
Type III glycogen storage disease - deb ranching enzyme alpha-1,6-glucosidase deficiency
Mild Von Gierke - gluconeuogenesis in tact
Normal blood lactate
67
Mcardle
Type V glycogen storage disease - Skeletal muscle glycogen phosphorylase
Muscle can't break down glycogen - painful muscle cramps w/ exercise and arrhythmia from electrolyte abnormalities.
Second wind from increased muscular blood flow.
68
Tay Sachs
AR
Deficiency hexosaminidase A --> Buildup of GM2 ganglioside
Progressive neurodegeneration, cherry-red spot on macula
69
Fabry
XR
Deficiency alpha-galactosidase A -->ceramics trihexoside
Early: Peripheral neuropathy, angiokeratomas, hypohidrosis
Late: progressive renal failure, cardiovascular DZ
70
Metachromatic leukodystrophy
AR
Arylsulfatase A --> Buildup of cerebroside sulfate
Central and peripheral demyelination w/ taxi, demention
71
Krabbe
AR
Deficiency galactocerebrosidase --> Buildup of galactocerebroside psychosine
Peripheral neuropathy, oligodendrocyte destruction, developmental delay, optic atrophy, globoid cells
72
Gaucher
AR - most common lysosomal storage disease
Deficiency glucocerebrosidase --> Buildup of glucocerebroside
hepatosplenomegaly, pancytopenia, osteoperosis, avascular necrosis of femur, bone crises, gaucher cells (lipid laden macrophage resembles tissue paper, looks like HUGE lymphocyte)
73
Niemann-pick
AR
Deficiency sphingomyelinase --> Buildup of sphingomyelin
hepatosplenomegaly, Progressive neurodegeneration, cherry-red spot on macula, foam cells (lipid laden macrophages)
NO MAN PICKS his nose with his SPHINGER
74
Hurler - Mucopolysaccharidoses
AR
Deficiency alpha-l-iduronidase --> Buildup of heparin sulfate, derma tan sulfate
developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
75
Hunter - Mucopolysaccharidoses
XR
Deficiency iduronate-2-sulfatase --> Buildup of heparin sulfate, derma tan sulfate
Mild hurler (developmental delay, gargoylism, airway obstruction, hepatosplenomegaly) + aggressive behavior
Hunters see clearly, aggressively aim for the X
76
Fatty acid metabolism
SYtrate = Synthesis - citrate shuttle --> fatty acid synthesis
CARnitine = CARnage - carnitine shuttle --> beta-oxidation
Long chain fatty acids require carnitine shuttle
77
Carnitine deficiency
Can't transport LCFA's into mitochondria --> toxic accumulation
Weakness, hypotonia, hypoketotic hypoglycemia (can't beta-oxidize LCFAs)
78
Medium chain acyl-CoA dehydrogenase deficinecy
Decreased ability to break down FA's in Acetyl CoA --> fatty acyl carnitines accumulate in blood with hypoketotic hypoglycemia.
Vomitting, lethargy, seizures, coma, liver dysfunction, hyperammonemia.
Sudden death in infants/children - avoid fasting.
79
Precursor to thyroid in diet
Phenylalanine --> tyrosine --> thyroid
Also precursor to DOPA, melanin, epi, and noreepie
80
Metachromatic leukodystrophy
Arylsulfatase A deficiency
Metachromasia: Sulfatides and cerebroside sulfate accumulate --> changes color of toluidine blue to reddish pink
Muscle weakness and difficulty walking - demyelinates central and peripheral nerves
81
Kcal/ carb, alcohol, and fatty acid
Carb - 4 kcal
Alcohol - 7 kcal
Fatty Acid - 9 kcal
82
Apolipoprotein E
Mediates remnant uptake - everything except LDL
83
Apolipoprotein A-I
Activates LCAT
84
Apolipoprotein C-II
Lipoprotein lipase cofactor that catalyzes cleavage
85
Apolipoprotein B-48
Mediates chylomicron secretion into lymphatics
Only particle originating in intestines
86
Apolipoprotein B-100
Binds LDL receptor
Only particle originating from liver
87
hormone sensitive lipase
Degrades TGs stored in adipocytes
88
Hepatic lipase
Degrades TGs remaining in IDL
89
LCAT
Catalyzes esterification of 2/3 of plasma cholesterol
90
Lipoprotein lipase
Degrades TGs circulating chylomicrons and VLDLs - on vascular endothelial surface
91
Pancreatic lipase
Degrade dietary TGs in small intestine
92
abetalipoproteinemia
AR
Chylomicrons, VLDL and LDL are absent
Deficient ApoB-48 and ApoB-100
Early: Severe fat malabsorption, steatorrhea, FTT.
Late: retinitis pigments, spinocerebellar degeneration (vit U deficiency), progressive ataxia, acanthocytosis
TX: restrict LCFAs and large doses of Vt E
93
hyperchylomicronemia
AR
Lipoprotein lipase or apolipoprotein C-II deficiency
Increased chylomicrons, TGs, and cholesterol
Pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas (norisk for atherosclerosis). Creamy layer in supernatant.
94
Familial hypercholesterolemia
AD
Absent/defective LDL receptors or ApoB-100
increased: IIa: LDL, cholesterol
IIb: LDL, cholesterol, VLDL
```
Heterozygotes (1:500) have cholesterol ≈ 300mg/dL; homozygotes (very rare) have cholesterol ≈ 700+ mg/dL.
Accelerated atherosclerosis (may have MI before age 20), tendon (Achilles) xanthomas, and corneal arcus.
```
95
Dysbetalipoproteinemia
AR - defective ApoE
Increased chylomicrons and VLDL
Premature atherosclerosis, tuberoeruptive xanthomas, palmar xanthomas
96
Hypertriglyceridemia
AD
Hepatic overproduction of VLDL
Increased VLDL and TG's in blood
Hypertriglyceridemia (> 1000 mg/dL) can cause acute pancreatitis. Related to insulin resistance.
97
Alpha amantin
found in death cap mushrooms - inhibits RNA polymerase II - causes liver failure
98
BRCA 1 and BCRA 2 chromosomes
BRCA 1 - 17
| BCRA 2 - 13
99
5 co-factors for alpha-ketoglutarate dehydrogenase complex and pyruvate dehydrogenase complex
B1, B2, B3, and B5, and lipoic acid
100
HLA A3
Hemochromatosis
101
HLA B8
Addison Dz, Myasthenia graves, graves disease
102
B27
Psoriatic arthritis, ankylosing spondylitis, IBD-associated arthritis, reactive arthritis
PAIR
103
DQ2/DQ8
Celiac - I 8 2 much gluten at DQ
104
DR2
Multiple sclerosis, hay fever, SLE, goodpasture
Multiple hay pastures have dit
105
DR3
DM I, SLE, graves, hashimoto, addison
2,3-SLE
106
DR4
Rhematoid arthritis, DM I, addison
107
DR5
Hashimoto
108
NK cells
kill viral and tumor infected cells w/ perforin/granzyme
Activity enhanced by !L-2, IL-12, IFN-alpha, IFN-beta.
Kills when MHC 1 is absent
109
T cell differentiation
Cortex - (+) selection - can bind self-MHC
Medulla - (-) selection - cells with high affinity binding undergo apoptosis.
Tissue-restricted self-antigens are expressed in the thymus due to the action of autoimmune regulator (AIRE); deficiency leads to autoimmune polyendocrine syndrome-1
110
Th1
Secretes: IFN-y
Function: activate macrophages and cytotoxic T cells to kill phagocyosed microbes
Induced by: IFN-y, IL-12
Inhibited by: IL-4 and IL-10 from Th2
Immune deficiency: mendelian susceptibility to mycobacterial disease
111
Th2
Secretes: IL-4, IL-5, IL-6, IL-10, IL-13
Function: activate eosinophils and promote IgE production
Induced by: IL-2. IL-4
Inhibited by: IFN-y (from TH1)
112
Th17
```
Secretes: IL-17, IL-21, IL-22
Function: immunity against extracellular microbes through induction of neutrophillic inflammation
Induced by: TGF-B, IL-1, IL-6
Inhibited by: IL-4, IFN-y
Immune deficiency: Hyper IgE syndrome
```
113
Treg
```
Secretes: TGF-B, IL-10, IL-35
Function: prevent autoimmunity by maintaining tolerance to self antigens
Induced by: TGF-B, IL-2
Inhibited by: IL-6
Immune deficiency: IPEX
```
114
IPEX
Immune dyregulation, polyendocrinopathy, enteropathy, x-linked syndrome
Genetic deficiency of FOXP3 --> autoimmunity
Characterized by enteropathy, endocrinopathy, nail dystrophy, dermatitis, and/or other autoimmune dermatologic conditions. Associated with diabetes in male infants.
115
Hepcidin
Decreases iron absorption (degrades ferroportin) and decreases iron release from macrophages -- > anemia of chronic disease
116
Complement pathways
Classic - IgG or IgM
Alternative - microbe surface molecule
Lectin - mannose or other sugar on cell surface
117
C3a, C4a, C5a
anaphylaxis
C5a - chemotaxis
118
C5b-9
MAC --> cytolysis
119
Opsonins
C3b and IgG
120
Inhibitors of complement activation
delay accelerating factor (DAF), and C1 esterase inhibitor prevent complement activation against self
121
Paroxysmal nocturnal hemoglobinuria
A defect in the PIGA gene preventing the formation of anchors for complement inhibitors, such as decay-acclerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59).
Causes complement-mediated lysis of RBCs.
122
IL-8
neutrophil chemotaxis
123
IL-12
Induces differentiation of T cells into Th1 cells. Activates NK cells.
124
TNF-a
Activates endothelium, causes WBC recruitment and vascular leak.
Causes cachexia in malignancy.
Maintains granulomas in TB.
IL-1, IL-6, TNF-α can mediate fever and sepsis.
125
IL-1
Causes fever, acute inflammation. Activates endothelium to express adhesion molecules. Induces chemokine secretion to recruit WBCs. Also known as osteoclast-activating factor.
126
IL-6
Causes fever and stimulates production of acute- phase proteins
127
Macrophages secrete
IL-1, Il-6, IL-8, IL-12, TNF-a
128
IL-2
Stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells.
129
IL-3
Supports growth and differentiation of bone marrow stem cells. Functions like GM-CSF.
130
IFN-y
Secreted by NK cells and T cells in response to antigen or IL-12 from macrophages; stimulates macrophages to kill phagocytosed pathogens. Inhibits differentiation of Th2 cells.
Also activates NK cells to kill virus-infected cells. Increases MHC expression and antigen presentation by all cells.
131
TH2 secrete
IL-4, IL-5, IL-10
132
IL-4
Induces differentiation of T cells into Th (helper) 2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG.
133
IL-5
Promotes growth and differentiation of B cells. Enhances class switching to IgA. Stimulates growth and differentiation of eosinophils.
134
IL-10
Attenuates in ammatory response. Decreases expression of MHC class II and Th1 cytokines. Inhibits activated macrophages and dendritic cells. Also secreted by regulatory T cells.
135
TGF-beta and IL-10
attenuate immune response
136
Chronic granulomatous disease
NADPH oxidase deficiency - unable to kill organisms with respiratory burst
137
Live attenuated vaccine
Pros: induces strong, often lifelong immunity.
Cons: may revert to virulent form. Often contraindicated in pregnancy and immunodeficiency.
Adenovirus (nonattenuated, given to military recruits), Polio (sabin), Varicella (chickenpox), Smallpox, BCG, Yellow fever, Influenza (intranasal), MMR, Rotavirus
“Attention! Please Vaccinate Small, Beautiful Young Infants with MMR Regularly!”
138
Killed vaccine
Pros: safer than live vaccines. Cons: weaker immune
response; booster shots usually required.
Rabies, Influenza (injection), Polio (Salk), hepatitis A
SalK = Killed RIP Always
139
Subunit vaccine
Pros: lower chance of adverse reactions.
Cons: expensive, weaker immune response.
HBV (antigen = HBsAg), HPV (types 6, 11, 16, and 18), acellular pertussis (aP), Neisseria meningitidis (various strains), Streptococcus pneumoniae, Haemophilus influenzae type b.
140
Toxoid
Pros: protects against the bacterial toxins.
Cons: antitoxin levels decrease with time, may require a booster.
Clostridium tetani, Corynebacterium diphtheriae
141
Hypersensitivities
```
Four types (ABCD):
A- Anaphylactic and Atopic (type I),
B- AntiBody-mediated (type II),
C- Immune Complex (type III),
D- Delayed (cell-mediated, type IV).
```
Types I, II, and III are all antibody-mediated.
142
Coombs tests
Direct Coombs test—detects antibodies attached directly to the RBC surface.
Indirect Coombs test—detects presence of unbound antibodies in the serum
143
Type II hypersensitivity
Cellular destruction: Autoimmune-hemolytic anemia, Immune thrombocytopenia, Transfusion reactions, Hemolytic disease of the newborn
Inflammation: Goodpasture syndrome, Rheumatic fever, Hyperacute transplant rejection
Cellular dysfunction: Myasthenia gravis, Graves disease, Pemphigus vulgaris
144
Arthus reaction
(type III hypersensitivity)
A local subacute immune complex-mediated (type III) hypersensitivity reaction. Intradermal injection of antigen into a presensitized (has circulating IgG) individual leads to immune complex formation in the skin. Characterized by edema, necrosis, and activation of complement.
145
Serum sickness
(type III hypersensitivity)
Fever, urticaria, arthralgia, proteinuria, lymphadenopathy occur 1–2 weeks after antigen exposure. Serum sickness-like reactions are associated with some drugs (may act as haptens, eg, penicillin) and infections (eg, hepatitis B).
The prototype immune complex disease. Antibodies to foreign proteins are produced and 1–2 weeks later, antibody- antigen complexes form and deposit in tissues --> complement activation --> inflammation and tissue damage.
146
Type 4 hypersensitivity
Response does not involve antibodies (vs types I, II, and III).
- contact dermatitis (eg, poison ivy, nickel allergy)
- graft-versus-host disease.
```
Tests (purpose): PPD (tuberculosis infection);
patch test (cause of contact dermatitis);
Candida extract (T cell immune function).
```
4T’s: T cells, Transplant rejections, TB skin tests, Touching (contact dermatitis).
147
Transfusion-related acute lung injury
Donor anti-leukocyte antibodies against recipient neutrophils and pulmonary endothelial cells.
Respiratory distress and noncardiogenic pulmonary edema.
Within 6 hours
148
Acute hemolytic transfusion reaction
Type II hypersensitivity reaction. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs).
Fever, hypotension, tachypnea, tachycardia, ank pain, hemoglobinuria (intravascular hemolysis), jaundice (extravascular).
Within 1 hour
149
Febrile non-hemolytic transfusion reaction
Two known mechanisms: type II hypersensitivity reaction with host antibodies against donor HLA and WBCs; and induced by cytokines that are created and accumulate
during the storage of blood products.
Fever, headaches, chills, ushing.
Within 1–6 hours
150
Anaphylaxis to transfusion
Type I hypersensitivity reaction against plasma proteins
in transfused blood. IgA- deficient individuals must receive blood products without IgA.
Urticaria, pruritus, fever, wheezing, hypotension, respiratory arrest, shock.
Within minutes to 2–3 hours
151
Anti-β2 glycoprotein
Antiphospholipid syndrome
152
ANA
nonspecific screening antibody - a/w SLE
153
Anticardiolipin, lupus anticoagulant
SLE, antiphospholipid syndrom
154
Anti-dsDNA, anti-Smith
SLE (anti-smith are against snRNPs)
155
Anti-histone
drug induced lupus
156
Anti-U1-RNP
Mixed connective tissue disease
157
Rheumatoid factor and anti-CCP
IgM Ab against fC of IgG
Rheumatoid arthritis
158
Anti-Ro/SSA, anti-La/SSB
Sjogren's Syndrome
159
Anti-Scl-70 (anti-DNA topoisomerase I)
Diffuse scleroderma
160
Anti-cetromere
Limited scleroderma - CREST syndrome
Calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia
161
Antisynthetase (anti-Jo-1) anti-SRP, anti-helicase (anti-Mi-2)
Polymyositis and dermatomyositis
162
Antimitochondrial 1° biliary cirrhosis
Antimitochondrial 1° biliary cirrhosis
163
Anti-smooth muscle
Autoimmune hepatitis type 1
164
MPO-ANCA/p-ANCA
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis (Churg- Strauss syndrome)
Ulcerative colitis
165
PR3-ANCA/c-ANCA
Granulomatosis with polyangiitis (Wegener)
166
Anti-phospholipase A2 receptor
1° membranous nephropathy
167
Antimicrosomal, antithyroglobulin, antithyroid peroxidase
Hashimoto
168
Anti-TSH receptor
Graves
169
IgA anti-endomysial, IgA anti-tissue transglutaminase, IgA and IgG deamidated gliadin peptide
Celiac
170
Anti-glutamic acid decarboxylase, islet cell cytoplasmic antibodies
Type I DM
171
Thymic aplasia (diGeorge)
Decreased T cells, decreased PTH, decreased Ca2+. Thymic shadow absent on CXR.
Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell de ciency), conotruncal abnormalities
Failure to develop 3rd/4th pharyngeal pouches - absent parathyroids and thymus
172
IL-12 receptor deficiency
Decreased Th1 response. Autosomal recessive.
Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.
Decreased IFN-γ.
173
Autosomal dominant hyper-IgE syndrome (Job syndrome)
Deficiency of Th17 cells due to STAT3 mutation --> impaired recruitment of neutrophils to sites of infection.
FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, increased IgE, Dermatologic problems (eczema). Bone fractures from minor trauma.
Increased IgE and eosinophils.
174
Ataxia telangiectasia
Defects in ATM gene --> failure to detect DNA damage --> failure to halt progression of cell cycle --> mutations accumulate; autosomal recessive.
Cerebellar defects (Ataxia), spider Angiomas (telangiectasia A ), IgA deficiency.
Increased AFP.
Decreased IgA, IgG, and IgE.
Lymphopenia, cerebellar atrophy.
Increased risk of lymphoma and leukemia.
175
Hyper IgM syndrome
Most commonly due to defective CD40L on Th cells --> class switching defect; X-linked recessive.
Severe pyogenic infections early in life; opportunistic infection with Pneumocystis, Cryptosporidium, CMV.
Failure to make germinal centers
176
Wiskott-Aldrich syndrome
Mutation in WASp gene; leukocytes and platelets unable to reorganize actin cytoskeleton --> defective antigen presentation; X-linked recessive.
WATER: Wiskott-Aldrich: Thrombocytopenia, Eczema, Recurrent (pyogenic) infections. Increased risk of autoimmune disease and malignancy.
Decreased to normal IgG and IgM
Increased IgE and IgA
Fewer and smaller platelets
177
Defective IL-2R gamma chain
Most common form of SCID (>ADA deficiency)
X-linked recessive
178
Leukocyte adhesion de ciency (type 1)
Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive.
Recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing, delayed (> 30 days) separation of umbilical cord.
neutrophils in blood. Absence of neutrophils at
infection sites.
179
Chédiak-Higashi syndrome
Defect in lysosomal trafficking regulator gene (LYST).
Microtubule dysfunction in phagosome-lysosome fusion; autosomal recessive.
PLAIN: Progressive neurodegeneration, Lymphohistiocytosis, Albinism (partial), recurrent pyogenic Infections by staphylococci and streptococci, peripheral Neuropathy.
Giant granules in granulocytes and platelets. Pancytopenia. Mild coagulation defects.
180
Chronic granulomatous disease
Defect of NADPH oxidase --> decreased reactive oxygen species) and defective respiratory burst in neutrophils; X-linked form most common.
Catalase (+) organism susceptibility
Abnormal dihydrorhodamine ( ow cytometry) test (green uorescence).
Nitroblue tetrazolium dye reduction test (obsolete) fails to turn blue.
181
Early complement deficiency
Infection w/ encapsulated species
Late complement (C5-C9) = Neisseria
182
T cell deficiency
fungal and viral infections
183
B cell deficiencies
bacterial infections
184
Hyperacute transplant rejection
W/in minutes -
Pre-existing recipient antibodies react to donor antigen (type II hypersensitivity reaction), activate complement
Widespread thrombosis of graft vessels, ischemia/necrosis.
Graft must be removed..
185
Acute rejection
Weeks-months
Cellular: CD8+ T cells and/or CD4+ T cells activated against donor MHCs (type IV hypersensitivity reaction).
Humoral: similar to hyperacute, except antibodies develop after transplant
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate. Prevent/reverse with immunosuppressants.
186
Chronic rejection
Months-years
CD4+ T cells respond to recipient APCs presenting donor peptides, including allogeneic MHC. type II and IV hypersensitivity reactions.
Recipient T cells react and secrete cytokinesproliferation of vascular smooth muscle, parenchymal atrophy, interstitial brosis. Dominated by arteriosclerosis.
Bronchiolitis obliterans (lung), Accelerated atherosclerosis (heart), Chronic graft nephropathy (kidney), Vanishing bile duct syndrome (liver)
187
Graft vs. host disease
Grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with “foreign” proteins --> severe organ dysfunction. Type IV hypersensitivity reaction
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly.
Usually in bone marrow and liver transplants (rich in lymphocytes).
Potentially beneficial in bone marrow transplant for leukemia (graft-versus-tumor effect).
188
Cyclosporine
Calcineurin inhibitor - prevents IL-2 transcription --> blocks T cell activation
Nephrotoxicity, hypertension, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism.
189
Tacrilomus (FK506)
Calcineurin inhibitor; binds FK506 binding protein (FKBP). Blocks T-cell activation by preventing IL-2 transcription.
SE's similar to cyclosporine (Nephrotoxicity, hypertension, hyperlipidemia, neurotoxicity), risk of diabetes and neurotoxicity; no gingival hyperplasia or hirsutism
190
Sirilomus (raoamycin
mTOR inhibitor; binds FKBP. Blocks T-cell activation and B-cell differentiation by preventing response to IL-2.
Used for kidney transplant rejection prophylaxis
SE's: pancytopenia, insulin resistance, hyperlipidemia; not nephrotoxic.
191
Basiliximab
MAB against IL-2R
Used for kidney transplant rejection prophylaxis
SE's: edema, HTN, tremor
192
Azathioprine
Antimetabolite precursor of 6-mercaptopurine. Inhibits lymphocyte proliferation by blocking nucleotide synthesis.
Cuases pancytopenia
Degraded by xanthine oxidase - toxicity increased by allopurinol.
193
Mycophenolate Mofetil
Reversibly inhibits IMP dehydrogenase, preventing purine synthesis of B and T cells.
SE's: GI upset, pancytopenia, hypertension, hyperglycemia. Less nephrotoxic and neurotoxic.
a/w invasive CMV
194
Glucocorticoids
Inhibit NF-κB. Suppress both B- and T-cell function by transcription of many cytokines. Induce T cell apoptosis.
SE's: Cushing syndrome, osteoporosis, hyperglycemia, diabetes, amenorrhea, adrenocortical atrophy, peptic ulcers, psychosis, cataracts, avascular necrosis (femoral head)
Demargination of WBCs causes artificial leukocytosis. Adrenal insufficiency may develop if drug is stopped abruptly after chronic use.
195
Glucose reabsorption
At PCT via Na/glucose cotransport
196
Glucosuria
Begins at plasma glucose ~200mg/dL
In pregnancy there in increased GFR and increased FF --> increased filtration of all substance --> glucosuria at normal plasma glucose
197
SGLT2 inhibitors
Sodium-glucose cotranporter 2 inhibitors - prevent glucose resorption in PCT
-flozin drugs
result in glycosuria <200mg/dl (pee out glucose)
198
Potter's sequence
Oligohydramnios (e.g. from renal agenesis)
limb deformities, facial anomalies, pulmonary hypoplasia
```
POTTER
Pulmonary hypoplasia
Oligohydramnios (trigger)
Twisted face
Twisted skin
Extremity defects
Renal failure (in utero)
```
199
Pronephros, mesonephros, metanephros
Pronephros—week 4; then degenerates.
Mesonephros—functions as interim kidney for 1st trimester; later contributes to male genitalia
Metanephros—permanent; 1st appears in 5th
week of gestation; nephrogenesis continues through weeks 32–36 of gestation.
200
Ureteric bud
Derived from caudal end of mesonephric duct;
gives rise to ureter, pelvises, calyces, collecting ducts; fully canalized by 10th week
201
ureteropelvic junction
Last to canalize --> most common site of obstruction (can be detected on prenatal ultrasound as hydronephrosis)
202
Ureter course
Under uterine artery/vas deferens
Over common iliac artery
Over iliac
Water (ureter) under the bridge (uterine artery/vas)
203
Renal clearance
Cx = (UxV)/Px = volume of plasma from which the substance is completely cleared per unit time.
Cx < GFR: net tubular reabsorption of X.
Cx > GFR: net tubular secretion of X.
Cx = GFR: no net secretion or reabsorption.
204
Effective renal plasma flow
can be estimated using para-aminohippuric acid (PAH) clearance, which is nearly 100% excreted
eRPF = UPAH × V/PPAH = CPAH
eRPF underestimates true renal plasma flow (RPF) slightly.
205
Renal blood flow
(RBF) = RPF/(1 − Hct).
Usually 20–25% of cardiac output. Plasma volume = TBV × (1 – Hct).
206
filtration fraction
FF=GFR/RPF
Normal is ~20%
207
Effect of prostaglandins and angiotensin II on arterioles
PDA - Prostaglandins Dilate Afferent
ACE - Angiotensin II Constricts Efferent
208
PCT
Reabsorbs all glucose and amino acids and most HCO3-, Na+, Cl–, PO43–, K+, H2O, and uric acid.
Generates and secretes NH3, which enables the kidney to secrete more CI H+.
PTH—inhibits Na+/PO43– cotransport --> PO43– excretion. H2O
AT II—stimulates Na+/H+ exchange --> increased Na+, H2O, and HCO3− reabsorption (permitting contraction alkalosis).
65–80% Na+ reabsorbed in PCT.
209
DCT
Reabsorbs NA/CL.
Impermeable to H2O - urine is fully dilute
PTH— Ca2+/Na+ exchange --> increased Ca2+ reabsorption.
5-10% of Na+ reabsorption
210
Thick descending loop
Passively reabsorbs H2O - concentrates urine making it hypertonic
211
Thick ascending loop
Reabsorbs Na+, K+, and Cl−.
Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through ⊕ lumen potential generated by K+ backleak.
Impermeable to H2O. Makes urine less concentrated as it ascends.
10–20% Na+ reabsorbed.
212
Collecting tubule
Reabsorbs Na+ by secreting K+ and H+ (regulated by aldosterone).
Aldosterone:
In principal cells: increase apical K+ conductance, increase Na+/K+ pump, increase epithelial Na+ channel (ENaC) activity --> lumen negativity --> K+ secretion.
α-intercalated cells: lumen negativity --> H+ ATPase activity --> increased H+ secretion --> increased HCO3−/Cl− exchanger activity.
ADH—acts at V2 receptor insertion of aquaporin
3–5% Na+ reabsorbed.
213
Renal tubular defects
Fanconi - PCT
Barter - Thick ascending limb
Gitelman - DCT
Liddle - collecting tubules
SIADH - collecting tubules
214
Fanconi syndrome
Generalized reabsorption defect in PCT --> excretion of amino acids, glucose, HCO3–, and PO43–, and all substances reabsorbed by the PCT
May lead to metabolic acidosis (proximal RTA), hypophosphatemia, osteopenia
Causes:
Hereditary defects (eg, Wilson disease, tyrosinemia, glycogen storage disease)
Ischemia,
Multiple myeloma,
Nephrotoxins/drugs (eg, ifosfamide, cisplatin, expired tetracyclines),
Lead poisoning
215
Bartter syndrome
Autosomal recessive
Resorptive defect in thick ascending loop of Henle (affects Na+/K+/2Cl– cotransporter)
Metabolic alkalosis, hypokalemia, hypercalciuria
Presents similarly to chronic loop diuretic use
216
Gitelman syndrome
Autosomal recessive
Reabsorption defect of NaCl in DCT
Metabolic alkalosis, hypomagnesemia, hypokalemia, hypocalciuria
Presents similarly to lifelong thiazide diuretic use, less severe than Bartter syndrome
217
Liddle syndrome
Autosomal dominant
Gain of function mutation --> increased activity of Na+ channel --> Na+ reabsorption in collecting tubules
Metabolic alkalosis, hypokalemia, hypertension, decreased aldosterone
Similar to hyperaldosteronism, but aldosterone is nearly undetectable
Treat with amiloride
218
RAAS activation
Decreased BP - renal baroreceptors
decreased NaCl delivery - macula dense
Increased sympathetic tone - beta-1 receptors
219
Angiotensin II
Vasoconstricts
Constricts efferent arteriole to preserve GFR with decreased RBF
Increases Na+/H+ activity in PCT for Na+, HCO3-. and H2O reabsorption
Increases aldosterone secretion --> Increased Na+ reabsorption and K+ secretion
Stimulates ADH release
220
Renin
Secreted by JG cells in response to:
- decreased renal perfusion pressure (detected by renal baroreceptors in afferent arteriole)
- increased renal sympathetic discharge (β1 effect)
- decreased NaCl delivery to macula densa cells
221
ANP/BNP
Released from atria (ANP) and ventricles (BNP) in response to increased volume
Acts as a “check” on RAAS
Relaxes vascular smooth muscle via cGMP --> increase GFR, and decrease renin.
Dilates afferent arteriole, constricts efferent arteriole, promotes natriuresis.
222
Calciferol - Vit D
PCT cells convert 25-OH vitamin D3 to 1,25- (OH)2 vitamin D3 (calcitriol, active form)
223
Dopamine in kidney
Secreted by PCT cells, promotes natriuresis.
Low dose: dilates interlobular arteries, afferent arterioles, efferent arterioles--> increase RBF, little
or no change in GFR.
High dose: acts as vasoconstrictor.
224
Parathyroid hormone in kidney
Secreted in response to↓ plasma [Ca2+], ↑ plasma [PO43–], or ↓ plasma 1,25-(OH)2 D3.
Causes ↑ [Ca2+] reabsorption (DCT),
↓ [PO43–] reabsorption (PCT),
↑ 1,25-(OH)2 D3 production
(↑ Ca2+ and PO43– absorption from gut via vitamin D).
225
Shifts K+ into cell
hypo-osmolarity
Alkalosis
beat adrenergic agonist (increase Na+/K+ ATPase)
Insulin (increase Na+/K+ ATPase)
Insulin shifts K+ into cells
226
Shifts K+ out of cell
Digitalis (blocks Na+/K+ ATPase)
HyperOsmolarity
Lysis of cells (eg, crush injury, rhabdomyolysis, tumor lysis syndrome)
Acidosis
β-blocker
High blood Sugar (insulin deficiency)
Succinylcholine (risk in burns/muscle trauma)
227
Hypokalemia
U waves and attened T waves on ECG,
| arrhythmias, muscle cramps, spasm, weakness
228
Hyperkalemia
Wide QRS and peaked T waves on ECG, arrhythmias, muscle weakness
229
Hypercalcemia
Stones (renal), bones (pain), groans (abdominal pain), thrones (urinary frequency), psychiatric overtones (anxiety, altered mental status)
230
Hypocalcemia
Tetany, seizures, QT prolongation, twitching (Chvostek sign), spasm (Trousseau sign)
231
Hypomagnesia
Tetany, torsades de pointes, hypokalemia, hypocalcemia (when [Mg2+] < 1.2 mg/dL)
232
Hypermagnesia
DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia
233
Hypophosphatemia
Bone loss, osteomalacia (adults), rickets (children)
234
Hyperphosphatemia
Renal stones, metastatic calci cations, hypocalcemia
235
Respiratory acidosis
HYPOVENTILATION
Airway obstruction
Acute or chronic lung disease
Opioids/sedatives
Weakening of respiratory muscles
236
Respiratory alkalosis
HYPERVENTILATION
```
Anxiety/panic attack
Hypoxemia (eg, high altitude)
Salicylates (early)
Tumor
Pulmonary embolism
```
237
Metabolic alkalosis
H+ loss/HCO3– excess
Loop diuretics
Vomiting
Antacid use
Hyperaldosteronism
238
Raised anion gap metabolic acidosis >12
```
MUDPILES
Methanol (formic acid)
Uremia
Diabetic ketoacidosis
Propylene glycol
Iron tablets or INH
Lactic acidosis
Ethylene glycol (oxalic acid)
Salicylates (late)
```
239
Normal anion gap metabolic acidosis
```
HARDASS
Hyperalimentation
Addison disease
Renal tubular acidosis
Diarrhea
Acetazolamide
Spironolactone
Saline infusion
```
240
Anion gap
= Na+ - (CI- + HCO3)
> 12 mEq/L is raise
8-12 is normal
241
Distal renal tubular acidosis - Type I
Inability of α-intercalated cells to secrete H+ --> no new HCO3– generated --> metabolic acidosis
Urine pH > 5.5 - hypokalemic
Amphotericin B toxicity, analgesic nephropathy, congenital anomalies (obstruction) of urinary tract, autoimmune diseases (eg, SLE)
Increased risk for calcium phosphate kidney stones
242
Proximal renal tubular acidosis
Defect in PCT HCO3– reabsorption --> increased excretion of HCO3– in urine --> metabolic acidosis
Urine can be acidified by α-intercalated cells in collecting duct, but not enough to overcome the increased excretion of HCO3–metabolic acidosis
Urine pH < 5.5 - hypokalemic
Cause: Fanconi syndrome, multiple myeloma, carbonic anhydrase inhibitors
Increased risk for hypophosphatemic rickets (in Fanconi syndrome)
243
Hyperkalemic tubular acidosis - Type 4
Hypoaldosteronism or aldosterone resistance; hyperkalemia--> decreased NH3 synthesis in PCT --> decreased NH4+ excretion
Urine pH < 5.5 (or variable) - hyperkalemic
Decreased aldosterone production (eg, diabetic hyporeninism, ACE inhibitors, ARBs, NSAIDs, heparin, cyclosporine, adrenal insuf ciency) or aldosterone resistance (eg, K+-sparing diuretics, nephropathy due to obstruction, TMP-SMX)
244
RBC casts
glomerulonephritis, hypertensive emergency
245
WBC casts
acute pyelonephritis, transplant rejection, tubulointerstitial inflammation
246
Fatty casts (oval fat bodies)
nephrotic syndrome - maltese cross sign
247
Granular casts
"muddy brown"
Acute tubular necrosis
248
Waxy casts
End-stage renal disease
Chronic renal failure
249
Hyaline casts
Nonspecific - concentrated urine samples
250
Nephritic syndrome
Due to GBM disruption.
Hypertension, ↑ BUN and creatinine, oliguria, hematuria, RBC casts in urine. Proteinuria < 3.5 g/day, but in severe cases may be in nephrotic range >3.5 g/day.
• Acute poststreptococcal glomerulonephritis
• Rapidly progressive glomerulonephritis
• IgA nephropathy (Berger disease)
• Alport syndrome
• Membranoproliferative glomerulonephritis
251
Nephritic-nephrotic syndrome
Severe nephritic syndrome with profound GBM damage that damages the glomerular filtration charge barrier → nephrotic-range proteinuria (> 3.5 g/day) and concomitant features of nephrotic syndrome.
Can occur with any form of nephritic syndrome, but is most commonly seen with:
• Diffuse proliferative glomerulonephritis
• Membranoproliferative glomerulonephritis
252
Nephrotic
Podocyte disruption → charge barrier impaired.
Massive proteinuria (> 3.5 g/day) with hypoalbuminemia, hyperlipidemia, edema. May be 1° (eg, direct podocyte damage) or 2° (podocyte damage from systemic process [eg, diabetes]).
• Focal segmental glomerulosclerosis (1° or 2°)
• Minimal change disease (1° or 2°)
• Membranous nephropathy (1° or 2°)
• Amyloidosis (2°)
• Diabetic glomerulonephropathy (2°)
253
FSGS
Most common nephrotic syndrome in African-Americans and Hispanics.
Can be 1° or 2° to other conditions (eg, HIV infection, sickle cell disease, heroin abuse, massive obesity, interferon treatment, or congenital malformations).
1° disease has inconsistent response to steroids. May progress to CKD.
LM—segmental sclerosis and hyalinosis B
EM—effacement of foot processes similar to minimal change disease
254
Membranous nephropathy
Can be 1° (eg, antibodies to phospholipase A2 receptor) or 2° to drugs (eg, NSAIDs, penicillamine,
gold), infections (eg, HBV, HCV, syphilis), SLE, or solid tumors.
1° disease has poor response to steroids. May progress to CKD.
LM—diffuse capillary and GBM thickening
IF—granular due to IC deposition
EM—“SPIKE AND DOME” appearance of subepithelial deposits
255
General details about nephritic
NephrItic syndrome = Inflammatory process.
Leads to hematuria and RBC casts in urine.
A/w azotemia, oliguria, hypertension (due to salt retention), proteinuria, hypercellular/inflamed glomeruli on biopsy.
256
Post strep glomerulonephritis
Adult prognosis is poor - kids is good
Type III hypersensitivity reaction.
Presents with peripheral and periorbital edema, cola-colored urine, HTN. ⊕ strep titers/serologies, decreased complement levels (C3) due to consumption.
LM—glomeruli enlarged and hypercellular A
IF—(“starry sky”) granular appearance (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition along GBM and mesangium
EM—subepithelial immune complex (IC) humps
257
Rapidly progressive (crescentic) glomerulonephritis
Poor prognosis, rapidly deteriorating renal function (days to weeks).
LM—crescent moon shape C . Crescents consist of fibrin and plasma proteins (eg, C3b) with glomerular parietal cells, monocytes, macrophages
Linear IF due to antibodies to GBM and alveolar basement membrane: Goodpasture syndrome— type II hypersensitivity reaction; Treatment: plasmapheresis
Negative IF/Pauci-immune (no Ig/C3 deposition): Granulomatosis with polyangiitis (Wegener)—PR3-ANCA/c-ANCA or Microscopic polyangiitis—MPO-ANCA/p-ANCA
Granular IF—PSGN or DPGN
258
Diffuse proliferative glomerulonephritis
Wire loops - lupus.
LM—“wire looping” of capillaries
IF—granular;
EM—subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
259
IgA nephropathy
Berge disease
```
Episodic hematuria that occurs concurrently with respiratory or GI tract infections (IgA is secreted by mucosal linings).
LM—mesangial proliferation
IF—IgA-based IC deposits in mesangium;
EM—mesangial IC deposition
```
260
Alport
Mutation in type IV collagen --> thinning and splitting of glomerular basement membrane.
X-linked dominant.
```
Eye problems (eg, retinopathy, lens dislocation),
glomerulonephritis, sensorineural deafness; “can’t see, can’t pee, can’t hear a bee.”
```
EM—“Basket-weave”
261
Membrano-proliferative glomerulonephritis
Nephritic syndrome, often co-presents with nephrotic syndrome.
Type I may be 2° to hepatitis B or C infection.
- Subendothelial IC deposits with granular IF
Type II is associated with C3 nephritic factor (IgG antibody that stabilizes C3 convertase --> persistent complement activation --> C3 levels).
- Intramembranous deposits, also called dense deposit disease
In both types, mesangial ingrowth --> GBM splitting“tram-track” appearance on H&E and PAS stains.
262
Ammonium magnesium phosphate stones
Radioopaque - coffin lid appearance
Also known as struvite; account for 15% of stones.
Caused by infection with urease ⊕ bugs (eg, Proteus mirabilis, Staphylococcus saprophyticus, Klebsiella).
Form staghorn calculi
Treatment: eradicate underlying infection, surgical removal of stone.
263
Uric acid stone
Rodiolucent - rhomboid
About 5% of all stones.
Risk factors: decreased urine volume, arid climates, acidic pH.
Strong association with hyperuricemia. Often seen in diseases withcell turnover (eg, leukemia).
Treatment: alkalinization of urine, allopurinol.
264
Cystine stones
Hexagonal stones
Hereditary (autosomal recessive) condition in which Cystine-reabsorbing PCT transporter loses function, causing cystinuria. Poor reabsorption of Cystine Ornithine, Lysine, Arginine (COLA).
Cystine is poorly soluble --> stones form in urine beginning in childhood.
Can form staghorn calculi.
Sodium cyanide nitroprusside test ⊕.
Treatment: low sodium diet, alkalinization of urine, chelating agents if refractory.
265
Wilms tumor
WT1 or WT2 (tumor suppressors) deletion/mutation on chromosome 11
Most common renal malignancy of early childhood
266
WAGR complex
Wilms tumor, Aniridia (absence of iris), Genitourinary malformations, mental Retardation/intellectual disability
WT1 deletion
267
Denys-Drash syndrome
Wilms tumor, Diffuse mesangial sclerosis (early-onset nephrotic syndrome), Dysgenesis of gonads (male pseudohermaphroditism)
WT1 mutation
268
Beckwith Weidemann syndrome
Wilms tumor, macroglossia, organomegaly, hemihyperplasia
WT2 mutation
269
Acute poststreptococcal glomerulonephritis
Subepithelial immune complex humps
270
Alport syndrome
Split basement membrane
271
Diffuse proliferative glomerulonephritis
“Wire looping” of capillaries
272
IgA nephropathy
Immune complexes in mesangium
273
Rapidly progressive glomerulonephritis
Crescent-moon shape
274
Membranoproliferative glomerulonephritis
“Tram-track” appearance on EM
275
Granulomatosis with polyangiitis (Wegener)
PR3-ANCA/c-ANCA
276
Microscopic polyangiitis
MPO-ANCA/p-ANCA
277
Nephrotic
Massive proteinuria (>3.5 g/day), hyperlipidemia, hypoalbuminemia, and edema.
278
Nephritic
Azotemia (increased BUN and Cr), oliguria, hypertension, and proteinuria <3.5 g/day.
279
Focal segmental glomerulosclerosis
Hyalinosis on LM
280
Membranous nephropathy
“Spike-and-dome appearance” on EM
281
Focal segmental glomerular sclerosis
most common cause of nephrotic syndrome in African Americans and Hispanics
282
CD14
on macrophages - binds Lipid A from bacterial LPS
283
Ma prophages in different tissues
Kupffer cells in liver, histiocytes in connective tissue, Langerhans cells in skin, osteoclasts in bone, microglial cells in brain
284
Fetal erythropoiesis occurs in:
Yolk sac (3–8 weeks)
Liver (6 weeks–birth)
Spleen (10–28 weeks)
Bone marrow (18 weeks to adult)
Young Liver Synthesizes Blood
285
Plummer-Vinson syndrome
(triad of iron de ciency anemia, esophageal webs, and dysphagia).
286
Diamond-Blackfan anemia
Short stature, craniofacial abnormalities, and
| upper extremity malformations (triphalangeal thumbs) in up to 50% of cases.
287
Warm Autoimmune hemolytic anemia
Warm (IgG)—chronic anemia
SLE and CLL and with certain drugs (eg, α-methyldopa)
288
Cold autoimmune hemolytic anemia
Cold (IgM and complement)—acute anemia triggered by cold;
CLL, Mycoplasma pneumoniae infections, and infectious Mononucleosis.
RBC agglutinates may cause painful, blue fingers and toes with cold exposure.
289
Lead poisoning
Defect: Ferrochelatase and ALA dehydratase
Accumulates: Protoporphyrin, ALA (blood)
290
Acute intermittent porphyria
Defect: Porphobilinogen deaminase, previously known as uroporphyrinogen I synthase (autosomal dominant mutation)
Accumulates: ALA, porphobilinogen
Painful abdomen, Port wine–colored urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs (eg, cytochrome P-450 inducers), alcohol, starvation
Treatment: hemin and glucose, which inhibit
ALA synthase.
291
Porphyria cutanea tarda
Defect: Uroporphyrinogen decarboxylase (autosomal dominant mutation)
Accumulates: Uroporphyrin (tea- colored urine)
Blistering cutaneous photosensitivity and hyperpigmentation
Most common porphyria. Exacerbated with alcohol consumption.
Associated with hepatitis C.
292
Bernard-Soulier syndrome
Defect in platelet plug formation.
Decreased GpIb --> defect in platelet-to-vWF adhesion.
Abnormal ristocetin test that does not correct with mixing studies.
293
Glanzmann thrombasthenia
Defect in platelet integrin αIIbβ3 (GpIIb/IIIa) --> defect in platelet-to-platelet aggregation, and therefore platelet plug formation.
Labs: blood smear shows no platelet clumping.
294
Hemolytic-uremic syndrome
thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure.
Shiga-like toxin of enterohemorrhagic E coli (EHEC) (eg, O157:H7).
HUS in adults does not present with diarrhea; EHEC infection not required.
Initial treatment of plasmapheresis.
295
Immune thrombocytopenia
Anti-GpIIb/IIIa antibodies --> splenic macrophage consumption of platelet-antibody complex. May be 1° (idiopathic) or 2° to autoimmune disorder, viral illness, malignancy, or drug reaction.
Labs: increased megakaryocytes on bone marrow biopsy.
Treatment: steroids, IVIG; rituximab or splenectomy for refractory ITP.
296
Thrombotic thrombocytopenic purpura
Inhibition or de ciency of ADAMTS 13 (vWF metalloprotease) decreased degradation of vWF multimers.
Labs: schistocytes, increased LDH, normal coagulation parameters.
Symptoms (FAT RN): pentad of Fever, microangiopathic hemolytic Anemia, Thrombocytopenia, Renal failure, Neurologic symptoms.
Treatment: plasmapheresis, steroids.
297
Types of hodgkin's lymphoma
Nodular sclerosis - Most common
Lymphocyte rich - Best prognosis
Mixed cellularity - Eosinophilia, seen in immunocompromised patients
Lymphocyte depleted - Seen in immunocompromised patients
298
Tumor Lysis Syndrome
Oncologic emergency triggered by massive tumor cell lysis, most often in lymphomas/leukemias.
Release of K+ --> hyperkalemia, release of PO43– --> hyperphosphatemia --> hypocalcemia due to Ca2+ sequestration by PO43–.
Nucleic acid breakdown --> hyperuricemia --> acute kidney injury.
Prevention and treatment include aggressive hydration, allopurinol, rasburicase.
299
HLA-DR3
Hashimotos
Anti-thyroid peroxidase (microsomal) and antithyroglobulin antibodies
300
Bicarbonate
Released by mucosal cells (stomach, duodenum, salivary glands, pancreas) and Brunner glands (duodenum)
Increased by pancreatic and biliary secretion with secretin
301
Pepsin
Released by chief cells (stomach) - Digests protein
Release increased by vagal stimulation (ACh), local acid
Pepsinogen (inactive) is converted to pepsin (active) in the presence of H+.
302
Gastric acid
Released by parietal cells - stimulated by histamine, vagal
stimulation (ACh), gastrin
Inhibited by by somatostatin, GIP, prostaglandin, secretin
303
Vasoactive intestinal polypeptide
Released from parasympathetic ganglia in sphincters, gallbladder, small intestine
Action: Increases intestinal water and electrolyte secretion and relaxation of intestinal smooth muscle and sphincters
Increased by distention and vagal stimulation
Decreased by adrenergic input
304
VIPoma
VIPoma—non-α, non-β islet cell pancreatic tumor that secretes VIP.
Watery Diarrhea, Hypokalemia, and Achlorhydria (WDHA syndrome).
305
Secretin
Released by S cells (duodenum)
Action: Increases pancreatic HCO3– secretion, decreases gastric acid secretion, increases bile secretion
Activated by acid, fatty acids in lumen of duodenum
Increased HCO3– neutralizes gastric acid in duodenum, allowing pancreatic enzyme to function
306
Cholecystokinin
Released by I cells in duodenum and jejunum
Action: Increases pancreatic secretion, gallbladder contraction, and sphincter of Odd relation. Dcreases gastric emptying
Activated by fatty acids and amino acids
307
Somatostatin
Released by D cells (pancreatic islets and GI mucosa)
Action: Decreases gastric acid and pepsinogen secretion, pancreatic and small intestine fluid secretion, gallbladder contraction, insulin and glucagon release
Increased by acid, decreased by vagal stimulation
Inhibits secretion of various hormones (encourages somato-stasis). Octreotide is an analog used to treat acromegaly, carcinoid syndrome, and variceal bleeding.
308
Hydralazine
Hypertension - pregnancy safe
Causes drug-induced lupus
Given w/ beta-blockers to avoid compensatory tachycardia
309
Nitroprusside
Treats hypertensive urgency - increases cGMP --> NO release
Cyanide toxicity
310
Fenoldopam
Dopamine D1 agonist --> vasodilation
Decrease BP increase naturesis
311
Milrinone
PDE-3 inhibitor
increase cAMP --> positive isotropy and chronotropy in heart
Vasodilation in vascular smooth muscle
312
Ezetimibe
Prevent cholesterol reabsorption in intestine brush border
313
Bile acid resins
Cholesteramine, colestipol, colesnvelam
Prevent intestinal reabsorption of bile acids
314
Fibrate
Gemfibrozil, bezafibrate, fenofibrate
Upregulate LPL --> increased TG clearance
Activate PPAR-alpha to in induce HDL synthesis
Increased risk of statin-induced myopathy and cholesterol gallstones
