Test 2 Flashcards
(157 cards)
1
Q
There are _ protein coding genes
A
19,000
2
Q
Point vs. frameshift vs. trinucleotide repeat mutations
A
Point: single base substitution
Frameshift: insertion or deletion altering reading frame
Trinucleotide: amplification of sequence of 3 nucleotides
3
Q
Most single nucleotide polymorphism are found _
A
Exons, introns or intergenic regions
4
Q
Polymorpism
A
Variation in just one nucleotide at a single site on the DNA molecule
5
Q
Epigenetic changes
A
Modulation of gene expression without altered DNA sequence
6
Q
Alterations in non-coding RNAs do what
A
Inhibit translation of their target messenger RNAs into their corresponding proteins
7
Q
The majority of autosomal dominant disorders create _
A
Outward physical changes
8
Q
Many autosomal dominant disorders exhibit _ onset. Even though _
A
Delayed age of onset
Even though mutant gene is present from birth.
9
Q
Example of aut. Dom. Disorder
A
Huntington disease
10
Q
Reduced or incomplete penetrance
A
Person has mutant gene but doesn’t or only partially expresses it phenotypically
11
Q
Variable expressivity
A
Trait is seen phenotypically in all individuals having mutant gene but is expressed differently among individuals
12
Q
De novo mutation
A
Affected individuals may not have affected parents, their disease arose from a new mutation
13
Q
Neurofibromatosis:
Genetic type
Penetrance
Prevalence
Expressivity
A
AD disease Nearly 100% penetrance (Everyone who has it will show it) 1/3,000 births High variable expressivity
14
Q
The largest group of Mendelian disorders
A
Aut recessive
15
Q
Many _ disorders present with enzyme defects that produce inborn errors of metabolism
A
Aut recessive
16
Q
Lyonization
A
> 75% of one X chromosome is randomly inactivated in all of the cells within a zygote
17
Q
Unfavorable lyonization
A
Inactivation of an abnormally high % of normal X, leading to clinical evidence of a recessive disease in a heterozygous female
18
Q
Oral-Facial-Digital syndrome is an example of a _
A
X-linked dominant
19
Q
Marfan syndrome
Genetic type Gene involved Tissue involved Clinical signs Prevalence
A
Autosomal dominant
FBN1 gene
Abnormal fibrillin, glycoprotein necessary for elastic fiber production
Tall, thin, long limbs/fingers, dislocation of lens,
1 in 5,000
20
Q
Ehlers-Danlos syndromes
How many types
Tissue affected
Clinical signs
A
At least 6 types Problem in collagen synthesis Hyperextensible skin, hypermobile joints Fragile skin, delayed wound healing Rupture of colon, large arteries Hernias
21
Q
Familial hypercholesterolemia
Classification Prevalence Mutated gene Effect on body Clinical signs
A
Mutation in receptor protein
1 in 500
Mutation in gene for LDL receptor
Impaired metabolism and increased LDL cholesterol
Xanthomas of skin, premature atherosclerosis
22
Q
Phenylketonuria
Genetic type of disorder
Prevalence
Lack of _ leads to excess _ which causes _
A
Autosomal recessive
1 in 10,000
Lack of phenylalanine hydroxylase leads to excess phenylalanine which causes mental retardation
23
Q
The two types of diseases caused by mutations in genes encoding enzyme proteins are
A
Phenylketonuria
Lysosomal storage diseases
24
Q
Lysosomal storage diseases:
Transmission
Affects who
Mechanism of disease
Effects
A
Autosomal recessive
Infants/young children
Accumulation of large insoluble molecules in macrophages leads to hepatosplenomegaly
CNS involvement, mental retardation, early death
25
Two large insoluble molecules that accumulate in lysosomal storage diseases
Sphingolipids
| Mucopolysaccharides
26
4 types of lysosomal storage diseases \
Tay-Sachs
Niemann-Pick
Gaucher
Mucopolysaccharidoses
27
4 Clinical signs of mucopolysaccharidoses
Coarse facial features
Clouding of cornea
Joint stiffness
Mental retardation
28
Hurler vs. hunter
Hurler:
AR
Deficiency of alpha-L-iduronidase
Treated with enzyme/marrow transplant
Hunter:
X-linked
Deficiency of L-iduronate sulfatase
Milder clinically
29
_ may underlie common diseases such as diabetes, hypertension, gout, schizophrenia, bipolar
Polygenic/multifactorial disorders
30
Prevalence of chromosomal abnormalities
1 in 200 newborns
31
Euploid vs. polyploidy vs. aneuploidy
Eu: normal, 46
Poly: 3 x 23 or 4 x 23
Aneu: 47, 45
32
Most common chromosomal disorder
Trisomy 21, Down syndrome
33
Turner syndrome
Partial/complete absence of one X chromosome
Short, webbed neck, low neck hairline, high palate, no 2˚ sex characteristics, amenorrhea
34
3 ways to diagnose genetic disease
FISH
Comparative genomic hybridization
Molecular diagnosis
35
When to do postnatal genetic analysis
```
Multiple congenital anomalies
Retardation
Aneuploidy
Sex chromosomal abnormality
Infertility
Multiple spontaneous abortions
```
36
_ creates a feeding ground for pseudomonas
Hypercholesterolemia
37
Three diseases caused by mutations in enzyme proteins
Phenylketonuria
Galactosemia
Lysosomal storage diseases
38
Mechanism of lead-induced anemia
Lead binds to enzymes involved in synthesis of hemoglobin
Blocks incorporation of iron into hemoglobin
Mycrocytic hypochromic anemia
39
Factors affecting clinical significance of thermal burns
% of body involved (rule of 9s)
Depth of burn
Internal injuries from inhalation
Age of pt
How fast and how well treated
40
Major cellular effects of radiation injury
Excitation and ionization of atoms and molecules
Causes DNA mutations
Produces free radicals
41
Differences b/t marasmus and kwashiorkor
M: deficiency of calories
Loss of muscle, growth stops
Emaciated
K: deficiency of protein, more severe than marasmus
Decreased albumin, loss of vascular on otic pressure
42
Clinical signs of vitamin A deficiency/toxicity
Vitamin C deficiency/toxicity?
Vit. A:
Def: impaired night vision, dryness of conjunctiva, keratinized lacrimal glands, squamous metaplasia of resp. And urinary tracts, common infections due to lowered immune sys.
Toxicity: nausea, vomiting, irritability, headache, anorexia, hair loss, dry skin
Vit. C:
Def: scurvy (impaired collagen synthesis), bleeding, hemorrhages, cartilaginous overgrowth, impaired wound healing, gingival bleeding, swelling, perio
Toxicity: possible kidney stones, rebound scurvy if stopping large doses, iron overload
43
CLADME
```
Conc.
Liberation
Absorption
Distribution
Metabolism
Excretion
```
44
How much aspirin can kill you
Kids: 2-4 gms
Adults: 10-30 gms
45
_ g of Tylenol causes _
15-20 g
| Liver damage
46
Cachexia
Wasting of cancer patients
47
Three phases of primary hemostasis
```
Adhesion
-platelets to damaged endothelial site
Activation
-vWF activates, platelets change shape
Aggregation
-fibrinogen/GP IIb/IIIa
```
48
Role of platelets and coagulation proteins in the formation of a clot
Coagulation proteins -> thrombin
Thrombin -> fibrinogen to fibrin (stability to clot)
Platelets are in primary hemostasis
49
Proteins responsible for regulating hemostasis, what do they do
Antithrombin
- inhibit activity of thrombin and other serine proteases (IXa, Xa, XIa, XIIa) by forming inactive enzyme-inhibitor complex
Antithrombin III - forms complex with thrombin to stop it from making fibrin monomers
Protein C
- regulates Va and VIIIa (cofactors of the coagulation cascade)
- deficiency results in hypercoagulability
Plasminogen
- converts to plasmin which breaks down cross-linked fibrin (breaks down clot)
50
Clinical and laboratory features of hemophilia A, B, and vW disease
```
A:
X- linked
Soft tissue bleeding
Prolonged PTT
Decreased Factor VIII
```
B:
X-Linked
Decreased factor IX
```
vW:
AD
Decreased amounts and/or abnormal production of protein
Mucocutaneous bleeding
Improve after adolescence
```
51
ITP vs. TTP
Immune thrombocytopenic purpura:
- Immune mediated destruction of platelets
Thrombotic thrombocytopenic purpura:
- intravascular platelet activation with formation of platelet rich microthrombi throughout circulation.
- deficiency of metalloproteinase ADAMTS 13
(Degrades big multimers of vWF)
- leads to accumulation of large vWF in plasma
52
Pathopohysiology and conditions that predispose to DIC
Uncontrolled activation of hemostatic system
Thrombin and plasmin formation.
Coagulation factors activated and consumed faster than they are made
Risk conditions:
Bleeding from multiple sites, thromboembolic problems, hypotension/shock, respiratory/hepatic/renal/CNS dysfunction, G- sepsis, tissue injury, snake bite, obstetrical complications, malignancies
53
Three components of the hemostasic system
Vascular wall
Platelets
Coagulation proteins
54
How does vascular injury activate hemostasis
Subendothelial collagen exposed
Platelet activation/plug
Coagulation proteins activated
Fibrin clot maintained/regulated
55
Intrinsic pathway
XII activated by kallikrein
XI activated by XIIa
XIa activated IX
56
Extrinsic pathway
Tissue factor activates VII
57
Common pathway
X -> Xa
Prothrombin -> thrombin
Fibrinogen -> fibrin
58
International normalized ratio
Patient PT time/control PT time
59
Partial thromboplastin time
Time it takes plasmin to form a clot in presence of added ground glass, cephalin, and calcium ions.
60
PT vs. PTT
PT initiates extrinsic
PTT initiates intrinsic
61
Thrombocytopenia vs. thrombocytosis vs. thrombocythemia
Penia: decrease in platelet number
| Cytosis/themia: increase in platelet number
62
Mixing studies
if PT or PTT is prolonged, mix 1:1 ratio of normal plasma and patient plasma
Should correct clotting time. If not, an inhibitor is present
63
```
Disorders of:
Primary hemostasis
Vs
Secondary hemostasis
Vs.
Regulatory system
```
1˚ - mucocutaneous bleeding, prolonged bleeding time, low RBC
2˚ - soft tissue bleeding, prolonged PT/PTT/thrombin time
Reg - soft tissue bleeding. Labs are normal
64
Factor VIII complex
Complex made of vWF and fac VIII procoagulant
65
vWD
Most common inherited bleeding disorder
Mucocutaneous bleeding
66
Mechanisms by which anemia can develop
Blood loss
- loss greater than RBC generation
- chronic hemorrhage
Decreased RBC survival
- hemolytic anemia (intrinsic, extrinsic)
Decreased RBC production
-
67
Intravascular hemolysis
Destruction of RBC within circulation
68
_ is a key feature of intravascular hemolysis
Decrease in serum haptoglobin
69
Causes of intravascular hemolysis
Transfusion rxn
Mechanical trauma
Decreased haptoglobin
70
Extravascular hemolysis
Destruction of RBC in reticuloendothelial system (spleen, liver)
71
3 Examples of extravascular hemolysis
Hereditary spherocytosis
Sickle cell anemia
Erythroblastosis fetalis
72
Intravascular hemolysis vs extravascular hemolysis
Intrinsic defects vs. extrinsic defects
Intra/extravascular is where the RBC is destroyed
In/extrinsic defects refer to where the defect that is causing anemia is
73
What happens to RBCs with a B12 or folate deficiency
DNA synthesis is delayed, mitotic division is delayed, nuclear size increases, makes abnormally large RBC, cells destroyed
74
Aplastic anemia:
Stem cell abnormality results in less hematopoiesis
75
What causes aplastic anemia
Unknown in over half of cases
Viruses, drugs, toxins have been implicated
76
Treatment of aplastic anemia
Bone marrow transplant
77
Myelophthisic anemia
Decreased RBC production due to replacement of marrow elements (tumor (multiple myeloma or metastatic cancer), or fibrosis)
78
Polycythemia:
What is it
Cause
Relative vs. absolute
Increase in red cell mass
Relative - dehydration, diuretics
Absolute -
1˚ non-regulated (neoplastic) proliferation of RBC and myeloid cells
2˚ stimuli increase erythropoietin
79
Polycythemia Vera
Non-regulated proliferation of red and myeloid cells
Part of primary absolute polycythemia
80
How to distinguish b/t primary and secondary polycythemia
Erythropoietin levels.
1˚ normal or suppressed levels
2˚ increased levels
81
Hodgkin vs. non-Hodgkin lymphoma
Hodgkin has:
- Reed Sternberg
- Fever
- Arises in a single/chain of nodes
- more common in young adults
- characterized by contiguous spread within lymph node
Non-Hodgkin:
- most of B cell origin
- more morphologic diversity
- multiple node involvement
- frequent extranodal spread
- peripheral blood involvement
- affect all ages
82
Features of Reed-Sternberg cell
Mirror image nuclei
Prominent nucleoli
Few RS cells in involved node
Can be seen in other disorders (mono), so to diagnose HD, RS have to be present in appropriate histologic background
83
Acute leukemia:
Clinical features
Pathologic features
Rapid, usually fatal
Mostly blasts (immature cells) in peripheral blood
White cell count often increased, but decreased in 30%
>20% blasts in bone marrow
84
Chronic leukemia:
Clinical
Pathological
Survive years
Mature cells in periphery
White cell count increased
Blasts not increased in bone marrow
85
How is a diagnosis of leukemia established
Terms of onset (acute/chronic)
Cell type (myeloid/lymphocyte)
86
Acute myelogenous vs. acute lymphocytic leukemia
ALL:
- Proliferating cell is lymphoid cell
- 40% of acute leukemias
- Most frequent type in kids <15
- Principle cause of cancer deaths in childhood
- 5 subtypes
- enlargement of lymph nodes, liver, spleen
- often involves CNS
AML:
- proliferating cell is primitive myeloid cell
- more common in adults
- several types of granules (myeloperoxidase) in mature myeloid cells
- Auer rods
- granulocytic sarcoma (soft tissue proliferation)
- bone marrow can cure
87
Lymphoma:
Leukemia:
Malignant proliferation of cells native to lymphoid tissue
Leukemia: malignant proliferation of cells native to bone marrow
88
HD therapy and prognosis is based on _
Stage
89
Treatment for HD
Combination of chemotherapy and radiotherapy
90
HD stages further divided into A and B. What do A and B mean
A: absence of systemic symptoms
B: presence of systemic symptoms
91
Why can acute leukemia develop after treating HD
Bone marrow toxicities of the chemotherapeutic drugs used
92
A lymphoma develops when there is a _ of lymphocytes that have been _ at a particular stage in transformation
Monoclonal expansion
| Arrested
93
All lymphoid neoplasms are considered to arise from _
Why?
A single transformed cell
The clonal cells proliferate without normal regulatory mechanisms
94
NHL is treated how
Chemo, and less often radiotherapy
95
CML vs CLL
CLL:
- mature appearing but incompetent lymphocyte
- monoclonal
- 95% B cell type
- IgM kappa
- 2/3 of chronic leukemias
- adults over 60
- 2:1 male female ratio
- chemo treatment
CML:
- immature hematopoietic cell
- increase in WBC count
- splenomegaly
- Philadelphia chromosome in proliferating cells
- fusion of BCR-ABL genes
- 25-60 yr old
- blast crisis
96
Clinical features of leukemia result from:
Clinical features:
Impairment of marrow function
Infiltration of body organs due to proliferation
Anemia, thrombocytopenia, infections, fever, organ enlargement, abdominal pain
97
Infiltration of gingiva is a feature commonly associated with _
Acute myelomonocytic leukemia
98
Plasma cell disorders result from _
Example?
Clonal expansion of ig secreting cells
Multiple myeloma
99
Multiple myeloma
```
Bence Jones (proteinuria)
70 yr old
IgG most common, then IgA
Multifocal destructive bone lesions
Bone resorption
Proteinaceous casts in kidneys
Hypercalcemia
```
100
Blood supply to lungs comes from two places:
Pulm
| Bronchial
101
_ produce surfactant
Type II pneumocystis
102
Defense mechanisms of lungs
Upper airway filter
Lower airway mucociliary
Lymphoid tissues - cellular and humoral immunity
Alveolar macrophages
103
COPD
Emphysema and chronic bronchitis
104
Emphysema
What is happening, how?
Perm enlargement of small air spaces from destruction of alveolar septa
Imbalance b/t protease and anti-protease enzymes
Caused by smoking
105
Centriacinar vs. panacinar
C: central portion of lobule, upper lobes, smoking
P: entire resp. Lobule, lower lobes, alpha-1-AT deficiency (smoking too)
106
What happens in bronchitis, how
Increased mucus glands, inflammation, fibrosis and narrowing of airways
Chronic irritation and infections
107
Bronchiectasis
Dilated distal bronchi due to obstruction, scarring, or other disorders
108
Atopic vs. non-atopic asthma
Atopic: extrinsic, environmental antigen
Non-atopic: initiated by infection, emotional stress, pollutants
109
Pathology of asthma
Mucus glands going nuts, smooth muscle hypertrophy, inflammation with eosinophils and type 2 helper cells
110
Pathogenesis of asthma
Antigen binds to surface IgE on mast cell releasing mediators
111
Treatment of asthma
Corticosteroids
| Bronchodilators
112
_ can cause pneumonia
Any organism in the right setting
113
What happens in bacterial pneumonia
```
Loss of cough reflex
Injury to cilia
Less phagocytosis
Pulm edema
Immunocompromised
```
114
Bronchopneumonia vs. lobar pneumonia
Broncho: patchy, begins around terminal bronchioles, very young and old
Lobar: involves entire lobe, 90% strep pneumoniae, healthy adults
115
Progression of pneumonia
Early, red hepatization: purulent exudate with many RBC
Later, grey hepatization: exudate with fibrin and macrophages
116
Viral/interstitial pneumonia is caused by
Virus or mycoplasma pneumoniae
117
Mycoplasma pneumoniae causes pneumonia that is:
Walking pneumonia, dry cough, fever
118
Dangerous aspect of atypical pneumonia (viral/interstitial)
Diffuse alveolar damage
119
ARDS
Rapid development
Same histologic features as interstitial pneumonia
Injury to endothelium (leaky) and alveolar epithelium
120
Mycobacterium tuberculosis
Causes TB
Acid fast, waxy coat
Infects 1/3 of world
Most common infectious cause of death in world
121
T/F TB can cause oral lesions
TRUE
122
Classic tissue reaction in TB
Caseating granuloma
123
Ghon lesion vs. ghon complex
Lesion is early, complex is after it has migrated
124
Cavitary TB
Where?
What happens?
Risks?
Apex
Significant scarring, can seed large airways, lymph nodes or blood
Direct extension to pleura
125
3 diseases that cause granulomatous inflammation
TB
Histoplasmosis
Sarcoidosis
126
Why is lung cancer sometimes misdiagnosed
Tumors can make hormone like substances
127
Pneumoconioses
Lung disorders caused by inhalation of dusts
128
Most dangerous particle size for pneumoconiosis
1-5 um
129
Most prevalent occupational disease in world
Silicosis (pneumoconiosis)
130
4 major parts of kidney, what they do
Glomeruli - network of capillaries b/t afferent and efferent arterioles
Tubules - reabsorption to form urine
Interstitium - collagen and blood vessels b/t tubules and glomeruli
Vasculature
131
Azotemia
Elevation of blood urea nitrogen (bun) and creatinine
Due to:
Decreased glomerular filtration rate
132
Uremia
Azotemia with more systemic clinical signs and symptoms like:
Gastroenteritis, peripheral neuropathy, pericarditis, dermatitis, hyperkalemia, metabolic acidosis
133
Acute nephrotic syndrome
From glomerular injury
Acute onset of HEMATURIA
Also some proteinuria, azotemia, and hypertension
134
Nephrotic syndrome
Heavy proteinuria, hypoalbuminemia, severe edema, hyperlipidemia, lipiduria
135
Acute renal failure = acute azotemia +
Oliguria/anuria
136
AD polycystic kidney disease
Features
Gene and protein
Multiple expanding cysts in both kidneys
Gradual renal failure
Urinary tract hemorrhage/infection
Aneurysms in circle of Willis
From PKD1 (encodes polycystin-1)
137
AR polycystic kidney disease:
Features
Gene
Kids
PKHD1 gene
Liver cysts, progressive liver fibrosis
Cysts in collecting tubules
138
2 mechanisms of glomerular injury
Immune complex deposits in glomerular basement membrane (mesangium)
Epithelial and endothelial injury
139
3 ways to evaluate kidney biopsies
Light micro - H+E stain, PAS, trichrome, jones stain
Immunofluorescence
Electron microscopy - identify immune complexes
140
What causes nephrotic syndrome
Increased glomerular capillary permeability to plasma proteins
141
4 types of nephrotic syndrome
Minimal change
- almost normal looking.
- Effacement of epithelial foot processes
Focal/segmental glomerulosclerosis
-partial sclerosis of glomeruli
Membranous nephropathy
- adults 30-50
- immune complexes in epithelial side of GBM
Diabetes mellitus
- minimal proteinuria progresses
- nodular glomerulosclerosis or kimmelstiel-wilson lesion
- hyaline arteriolosclerosis, atherosclerosis, nephrosclerosis
142
3 parts to nephrotic syndrome
Hematuria
Oliguria and azotemia
Hypertension
143
Acute postinfectious (poststreptococcal) glomerulonephritis is a type of _
Features?
Nephritic syndrome
Infiltration of neutrophils and monocytes, immune complexes in GBM and sometimes mesangium
144
IgA nephropathy is a type of _
Features
Nephritic syndrome
Children/young adults
Hematuria 1-2 days after URT viral infection
Increased IgA
henoch-Schonlein purpura
145
Rapidly progressive glomerulonephritis is consistent with _
Characteristic finding
Nephritic syndrome
Crescentic glomerulonephritis
146
Acute pyelonephritis is secondary to _
UTI
147
```
Arterionephroslcerosis
Contributing factors
Leads to?
Pathology
Histo
```
Hypertension, diabetes
Leads to chronic renal failure
Reduction in size of kidneys
Narrowing of lumens, tubular atrophy, sclerosis of glomeruli
148
Thrombotic microangiopathies:
1. thrombotic thrombocytopenia purpura (TTP)
Acquired defect in _ that does _
2. Hemolytic uremic syndrome:
Endothelial cell injury from _
ADAMTS 13, protease that degrades vWF multimers
Shiga-toxin from E. coli or shigella
149
Most frequent site of stone formation
Calyces and pelvis
150
3 types of stones
Ca
Mg ammonium phosphate
Uric acid
151
Renal cell carcinoma arise from _ and can come from having _ syndrome
Tubular epithelium
Hippel-lindau
152
Wilm’s tumor:
In who
Pathology
Kids 2-5
| Triphasic proliferation of cells (epithelial, stromal, blastemal components)
153
Prothrombin time
Measurement of clot time of plasma
Added thromboplastin and Ca2+
153
4 intrinsic defects that cause hemolytic anemia, explain them
Membrane defects - RBC membrane is less deformable and is destroyed by spleen
Abnormal hemoglobin (sickle cell) - hemoglobin gels when deoxygenated, destroyed by spleen, can block circulation
Lack of globin chains - thalassemia - absent alpha or beta globin chains of hemoglobin. Less globin = less hemoglobin -> anemia
Metabolic defect - G6PD deficiency - red cells susceptible to oxidant injury by drugs or toxins. Less flexible RBC, extravascular hemolysis
153
Three extrinsic defects causing hemolytic anemia, examples and explain
Immune destruction
- Erythroblastosis fetalis - blood group incompatibility b/t mother and fetus.
- Hemolytic transfusion rxn
- autoimmune hemolysis - antibodies to own blood
Mechanical trauma
-cardiac valve prosthesis - abnormal valve damages RBC
Infection
-malaria - parasites infect RBC, cause lysis of RBC
153
Most common cause of anemia worldwide
Iron deficiency
153
Which purine base needs B12 and folate as cofactors
Thymidine
