Pathoma Flashcards
1
Q
Describe the difference between hypertrophy and hyperplasia
A
Hypertrophy is the increase in gene activation, protein synthesis, and production of organelles.
Hyperplasia is the production of new cells from stem cells. Permanent cells cannot undergo hyperplasia. (Cardiac, Skeletal muscle, nerves)
2
Q
How are cells decreased in size?
A
Ubiquitin proleosome degradation.
3
Q
MetaplasiA
A
stress causes a change in cell type.
Barretts esophagusnon keratinized squamous to columnar in response to stomach acid.
4
Q
In addition to cell stress, which vitamin deficiency can lead to metaplasia?
A
Vitamin A deficiency
Important in differentiation of specialized epithelial structures such as the eye.
5
Q
Aplasia
A
Failure of cell production during enibryogenesis.
6
Q
Describe the difference between slowly developing cell injury and acute injury in regard to ischemia.
A
Slow developing ischemia results in atrophy. Think renal artery atherosclerosis.
Acute ischemia results in cell injury (renal artery embolus)
7
Q
Hypoxia
A
Low oxygen in the tissue.
Impairs ATP production leading to cellular injury.
8
Q
Hypoxemia
A
Low Oxygen in the blood.
Normally it is 60 mm Hg. and 90% sat.
Think of high altitude.
Diffusion defects
V/Q mismatches
Decreased carrying capacity.
9
Q
Cherry red appearance of the skin.
A
Carbon monoxide poisoning.
10
Q
Iron in the blood is oxidized to Fe3+
A
Methemoglobinemia.
Seen with sulfa/nitrate drugs in new borns.
Treat with intravenous methylene blue.
11
Q
Cyanosis with chocolate colored blood.
A
Methemeglobin
Treat with methylene blue.
12
Q
What is the hallmark of reversible cellular injury?
A
Cellular swelling with loss of microvilli and membrane blebbing.
Think initial hypoxia.
13
Q
What is the hallmark of irreversible cellular injuries?
A
Membrane damage.
Cytoslic enzyme leakage (cardiac troponin)
Cytochrome C leaking into cytosol from mitochondria activating apoptosis.
14
Q
What is the morphologic hallmark of cell death?
A
Loss of the nucleus.
Nuclear condensation (pyknosis)
Fragmentation
Dissolution
Two mechanisms of cell death are necrosis and apoptosis.
15
Q
Necrotic apoptosis
A
Necrotic tissue remains firm.
Characteristic of infarction of all organs except the brain (liquefactive)
16
Q
Liquefactive necrosis
A
Liquid necrosis via cell lysis.
Brain lysis from microglial cells.
Abscesses from neutrophil enzymes.
Pancreatitis from pancrease enzymes.
17
Q
Gangrenous necrosis
A
Coagulative necrosis
following ischemia of lower limb and GI.
Can be wet when there is an infection leading to liquefactive.
18
Q
Caseous necrosis
A
Soft, cotage cheese like.
Combination of coagulative and liquefactive.
Very related to fungal infections and TB.
19
Q
Fat necrosis
A
Chalky white necrotic adipose tissue due to calcium deposit.
Characteristic of trauma to fat. Trauma to breast etc.
20
Q
Difference between dystrophic calcification and metatastic calcification.
A
Dystrophic occurs when there is necrosis and calcium binds to it.
Metatastic is due to excessive serum calcium levels leading to calcium deposits in normal tissue.
21
Q
Fibrinoid necrosis
A
Necrotic damage to blood vessel wall.
Leads to exudate and bright staining of vessel wall.
Think hypertension and vasculitis.
22
Q
How does the cytoplasm change with apoptosis?
A
Becomes eosinophilic (pink) and shrinks.
Proteins break down and the nucleus condenses.
Capsases then induce cellular injury and DNA damage.
23
Q
What is the intrinsic mitochindrial apoptotic pathway?
A
Cellular injury, DNA damage or loss of hormonal stimulation leads to activation of Bc12.
Cytochrome c leaks out of inner mitochondrial matrix and activates capsases.
24
Q
What is the extrinsic mitochondrial apoptotic pathway?
A
FAS ligand binds FAS death receptor on target cell activting capsases.
Tumor necrosis factor TNF can also bind leading to capsase activity.
25
How do CD8 cells trigger apoptosis
Perforins secreted
| Granzyme enters pores from perforins and activate capsases.
26
how do free radicals cause cellular injury?
Peroxidation of lipids and oxidation of DNA/proteins.
27
What are the main antioxidants?
Glutathione
| Vitamins A, C, and E.
28
Describe reperfusion injuries
return of blood to ischemia tissus results in the production of o2 derived free radicals that damage tissue.
Myocardial tissue will continue forming cardiac enzymes following reprofusion.
29
What are the common characteristics of amyloid?
Beta pleated sheets
Congo red staining
Apple-green birefringence under polarized light.
30
How will amyloid effect the kidneys?
Nephrotic syndrome
| The kidney is the most common organ involved in amyloidosis.
31
What role does amylin have in type I diabetes?
Aniylin derived from insulin deposits into the beta islets of the pancrease.
32
Describe the role of amylin in alzhimers disease.
Amyloid deposits in the substantia nigrae (basal ganglia) in the midbrain.
33
What happens when a TLR is activated on a macrophage?
Leads to the upregulation of NF-kB which is a nuclear transcription factor that leads to production of immune mediators.
34
What role do prostaglandins have in inflammation?
Increase vascular permeability and pain.
35
What role do leukotriens have in inflammation?
These attract neutrophils
Mediate vasoconstriction
Bronchospasm
Increase vascular permeability.
36
What do mast cells release?
Histmine immediately leading to vasodilation and increased vascular permeability. (IgE)
Leukotriens are released as well in the delayed response.
37
Classic pathway of compliment
IgG or IgM mediated
38
Alternative pathway of complement
Microbrial products directly activate complement.
39
Mannose- binding lectin pathway
MBL binds to mannose on pathogen activating complement.
40
What do all three compliment pathways produce?
All three will produce C3 convertase that activate C5 .
C5 combines with 6-9 to form the MAC (attack complex)
41
Describe C3a and C5a
C3a and C5a both trigger mast cell histamine release.
C5a further chemoattracts neutrophils.
42
Hageman factor
Factor 12 relased by the liver that is activated by tissue collagen.
When activate starts coagulation and fibrinolytic systems, complement, and the kinin system.
43
Cardinal signs of inflammation
```
Rubor
Calor
Dolor
tumor
Loss of function
```
44
How is fever mediated?
Pyrogens cause macrophages to release IL-1 and TNF which increase COX activity in hypothalamus.
Raises the temp set point.
45
What allows neutrophils to roll?
Selectins
P-selectin = histamine
E selectin = TNF and IL-1
46
What allows neutrophils to perform adhesion?
ICAM and VCAM interacting with integrins.
47
Pt shows increased bacterial infections that lack pus, had a delayed separation from the umbilical cord at birth and increased circulating neutrophils.
Likely a neutrophil adhesion mutation in the integrins.
48
What enzyme allows for oxidative bursts?
NADPH interacting with O2
49
Chronic granulomatous disease?
Characterized by poor O2 dependent killing due to a deficiency in the NADPH oxidase defect.
Heavily suceptible to catalase positive critters!
Can test with the nitro blue tetrazolium test.
50
What are the antiinflamatory cytokines produced?
IL-10 and TGF
51
Which cytokine by macrophages recruits more neutrophils?
IL-8
52
Describe CD4 cell activation
APC cells present on MHCII
B7 on APC binds CD28 on CD4 cells.
53
What do TH1 cells secrete
CD4 cells that secrete IL-2 which is a Tcell growth factor and CD8 T cell activator.
Also secrete IFN gamma that activates macrophages.
54
What do TH2 cells secrete
CD4 cells that secrete IL-4 for B cel switch to IgG and IgE.
IL-5 which is for eosinophils and plasma cell maturation.
And IL-10 that inhibits TH1 phenotype.
55
what is the second activation factor for CD8 cells?
First is MHC1 interaction.
Second is IL-2 from CD4 TH1 cells.
then they are good to go NAVY SEAL.
56
What do all naive B cells have?
All have IgM and IgD
57
How do T helper clls interact with B cells?
T helper cells bind B cells via CD40 receptor binding the CD40L on the T helper cell.
In addition, the T helper cell secretes IL-4 and IL-5 to mediate B-cell isotype switching and plasma cell maturation.
58
what makes sure that granulomas around TB remain intact?
IFN-gamma from TH1 cells.
Converts macrophages to epitheliod histiocytes and giant cells that wall off the infection.
59
What is Digeorge syndrome?
Developmental failure of the third and fourth pharyngeal pouches.
22q11 microdeletion presenting with lack of thymus, hypocalcemia, and abnormalities of the heart, great vessels, and face.
60
What is Severe combined immunodeficiency?
| SCID
Defective cell mediated and humoral deficiency.
Cytokine receptor defects
Adenosine deaminase deficiency
MHC II deficiency
Need to bubble baby this person and use stem cell transplant.
61
What is X-linked agamma globulinemia?
complete lack of immunoglobulin due to error in B-cell maturation.
Mutated tyrosine kinase.
62
What happens if there is an IgA deficiency?
Most common immunoglobulin deficiency.
Results in increased risk for mucosal infections especially viral.
63
What is Wiskott Aldrich syndrome?
Thrombocytopenia, eczema and recurrent infections do to a MUTATION IN THE WASP GENE X-LINKED.
Defective humoral and cellular immunity.
64
If one were deficient in C5-C9 compliment what are they at increase risk for infection of?
Neisseria infections!
65
what is seen when there is a C1 inhibitor deficiency?
Hereditary angiodema.
Beware of ACE inhibtors in these patients as edema of lips and skin can occur.
66
What is T cell negative selection.
The removal of self reactive T cells. Occurs in the thymus or bone marrow or become anergic.
67
What is Libman Sacks endocarditis?
Classic finding in lupus patients.
Small sterile deposits on both sides of the mitral valve.
68
What are lupus patients have mutation in?
Characteried by antinuclear antibody ANA (sensitive but not specific) and anti dsDNA antibodies (highly specific)
69
Which three drugs are common agents of drug induced lupus?
Hydralazine
Procainamide (Class 1A)
Isoniazid (RIPE therapy)
Cause lupus through antihistone antibodies.
70
What is Sjorgren syndrome?
Autoimmune destruction of the lacrimal and salivary glands. Characterized by ANA antibodies.
Type IV mediated (lymphocye mediated Delayed response)
Look for dry eyes (keratoconjuctivitis), dry mouth (xerostomia) and recurrent dental carries in older women.
71
Which lymphoma are Sjorgren syndrome patients at risk for?
B cell lymphoma.
72
What is scleroderma?
Autoimmune tissue damage with activation of fibroblasts and deposition of collagen.
Can be difuse or localized and almost any organ can be involved although the esophagus is most common.
Characterized by ANA and anti-DNA topoisomerase (Scl-70) antibody.
Prototype for localized is CREST syndrome with calcinosis, anti centromere antibodis, raynauds, esophageal dysmotility etc.
73
Describe the difference between labile, stable and permanent tissues.
Labile tissues possess stem cells and can reheal readily. (Small and large bowel, skin, bone marrow)
Stable tissue are quiescent tissues that can regenerate when needed (ex: Liver regeneration after hemisection)
Permanent tissue cannot regernate (myocardium, skeletal muscle, and neurons)
74
Which type of collagen is immediately layed down following an injury?
Type III collagen.
Later replaced with the high tensile strength type I collagent.
in order to remove type III collagen zinc is required as a cofactor.
75
What is the major mediator of tissue regeneration and repair?
TGI-alpha which is an epithelial and fibroblast growth factor.
76
what is primary and secondary intention healing?
Primary is when the wound edges are brought together via suturing.
Secondary intention involves the edges not being approximated. Granulation tissue fills the defect and myofibroblasts contract the wound forming a scar.
77
Why is vitamin C essential in scar formation?
It is needed to hydroxylate proline and lysin procollagen residues to allow for collagen cross linking.
Copper plays a role in cross linking as well.
Collegenase requires zinc to remove type III collagen after Type I tensile is layed down.
78
what collagen type is in excess during keloid formation?
Type III collagen excess.
79
Most common cause of cancer mortality in adults
Lung
Prostate/breast
Colorectal
80
what are the high risk HPV strains?
16,18,31,33
81
How does non ionizing radiation cause cell problems?
Sun rays
| results in pyridine dimers in DNA normally excised from restriction endonuclease.
82
Describe the function of Ras
When bound to GTP it sends growth signals to the nucleus.
It normally inactivates itself.
Thus if its constantly on = increased growth factors.
83
What is the purpose of cyclins?
Cyclins and cyclin dependent kinases form a complex which phosphorylates proteins that drive the cell through the cell cycle.
84
what are the two tumor supression genes?
P53 and Rb (retinoblastoma) act to supress the risk of tumor supression.
85
Which stage of the cell cycle does p53 regulate?
Stops G1 from entering the S phase.
If there is DNA damage p53 stops the cells cycle and upregulates repair enzymes.
If it cannot be repaired p53 will induce apoptosis through the BAX pathway
86
C-myc mutation
Burkitt lymphoma
87
N-myc mutation
Neuroblastoma
88
L-myc mutation
Lung carcinoma
| Transcription factor.
89
Describe how p53 can cause apoptosis.
p53 will upregulate the BAX
BAX disrupts Bcl12 allowing protein C to leak out of the mitochondria
90
What cell cycle stage is regulated by Rb
G1 to S phase by holding onto E2F transcription factor.
When its phosphorylated by cyclin D/ Cyclin dependent kinase 4 it will release E2F allowin cell cycle progression.
91
Which type of lymphoma is Bcl2 overexpressd?
Follicular lymphoma.
Thus bcl2 cannot be released from the mitochondria inhibiting the release of cytochrome c apoptosis factor.
92
What role does telomerase play in cell cancers?
Telomerase is generally upregulated preservin the telomeres.
FGF and VEGF are upregulated as well allowing for angiogenesis.
93
What occurs when E-Cadherins are down regulated in cancer?
These normally keep cells conjoined adjacently.
when down regulated metastasis can occur.
94
What type of collagen holds cells down to the baement membrane?
Type 4
95
What is lematrogenous cancer spread?
Common to sarcomas.
| Invades the blood supply.
96
Which carcinoma is characterized by seeding of body cavities?
Ovarian.
Makes sense as it involves the peritoneum.
97
what is the most important prognostic marker for cancer patients?
```
Staging is key.
Far more important than grading.
T - Tumor size/depth
N - Tumor spread
M - Metastasis (important)
```
98
What is the difference between primary and secondary hemostasis?
Primary forms a platelet plug between the platelets and the vascular wall.
Secondary hemostasis stabilizes the platelet plug and is mediated by the hemostasis cascade.
99
Describe the steps of primary hemostasis.
Transient vasoconstriction via endothelin.
Platelets hook onto vWF sing GP1b.
Platelets release ADP promoting GPIIb/IIa binding and thromboxane via COX is released promoting aggregation and the primary plug.
100
what are the most common clinical signs of primary hemostasis disorders?
Mucosal and skin bleeding.
Look for petechiae and echymoses as well as purpura.
101
What are normal platelet ammounts?
150,000-400,000
<50,000 leads to symptoms.
102
What is immune thrombocytopenic purpura?
Autoimmune production of IgG against platelet antigens GPIIb/IIIa.
Most common form of thrombocytopenia in adults and children.
103
what is microangiopathic hemolytic anemia?
RBC are sheared as they cross microthrombi from platelets resulting in anemia with schistocytes.
104
What is Bernard Soulier syndrome?
Degect in GPfb thus platelet adhesion is impaired.
Look for a blood smear with thrombocytopenia and enlarged platelets.
105
Describe what would happen if there was a deficiency in GPIIB/GPIIIa
Platelet aggregation would be impaired.
106
How do NSAIDS disrupt platelet aggregation.
Inhibit the formation of thromboxane from COX.
107
What factor is required for the extrinsic clotting pathway vs the intrinsic?
Extrinsic requires factor 12
Intrinsic requires factor 7
108
What does PT measure?
Factor 7 and common factors
| 2,5, 10, and fibrinogen.
109
What does PTT measure?
Measures intrinsic factors
12,11,9,8
and common factors 1, 5, 10 and fibringen.
110
What is hemophilia A?
Genetic factor 8 deficiency.
It is X linked recessive mostly in males.
Look for deep tissue joint and post surgical bleeding.
111
How would PT and PTT be effected in someone with hemophilia A?
This is lack of Factor 8 clotting
Thus the extrinsic PTT would be prolonged with a normal PT.
112
What is seen in Von Willebrand disease?
Genetic vWF deficiency.
Most common inherited coagulation disorder
Impaired platelet binding, mild mucosal and skin bleeding.
Increase PTT bleeding time and a normal PT.
Keep in mind that VWF carries factor 8.
113
What is the treatment for von willebrand disease?
Desmopressin (ADH analog) which increases vWF release from Weibel palade bodies of the endothelial cells.
114
Which factors require vitamin K?
Factors 2, 7, 9, and 10 as well as proteins C and S.
Very common in newbords due to a lack of GI colonization by bacteria that normally synthesize vitamin K. Thus prophylatic vitamin K injections are norm.
115
What is disseminated intravascular coaulation?
Pathological activation of the coagulation cascade.
Leads to widespread microthrombi resulting in ischemia and infarction.
Lab values show decreased platelet count as well as increased PT and PTT times.
D-dimer will be extremely high as well.
116
What is the best screening test for DIC?
D-dimer.
Derived from splitting of cross linked fibrin; D-dimer is NOT produced from splitting of fibrinogen.
117
What does tissue plasminogen activator tPA do
Converts plasminogen to plasmin.
Plasmin cleaves fibrin and serum fibrinogen destroying coagulation factors and blocking platelet aggregation.
118
Patient comes in with increased PT and PTT, platelets however are in normal range.
D-dimer is in the normal range.
This is excessive tpa produced lysing all clots.
Treatment is aminocaproic acid.
119
Aminocaproid acid
Drug used to block the activation of plasminogen in the circumstance of excessive clot busting.
120
Lines of Zahn consist of?
These are deeply related to deep venous thrombosis.
Include layers of platelets/fibrin and RBC attached to vessel walls.
This is highly indicative of thrombosis.
121
What does protein C inactivate?
Factors 5 and 8
122
What is elevated in vitamin B12 and folate deficiency?
Homocysteine becomes elevated this can lead to increased rsk for thrombosis.
123
What is factor 5 Leiden?
Mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S.
124
why is birth control use related to hypercoagubility?
Estrogen induces increased production of coagulation factors, therby increasing the risk for thrombosis.
125
When are gas emboli seen?
Seen when nitrogen gas percipitates out of the blood in divers.
126
What is the Bends?
Gas embolus causing joint and muscle pain in divers.
127
Where do systemic emboli usually originate
The left heart
| Travel down systemic circulation to occlude flow to organs most commonly in the lower extremities.
128
What is mean corpuscular volume?
| MCV
Microcytic MCV < 80
Normocytic 80-100
Macrocytic >100
Just think of what scores on an exam would be acceptable.
129
Why does microcytic anemia occur?
Decreased production of hemoglobin or protoporphyrin.
Bone marrow problems in hemoglobin division.
130
What is the most common type of anemia?
Microcytic due to lack of iron.
131
What is the function of ferroportin?
Enterocytes transport iron across the cell membrane into blood via ferroportin.
132
What is the function of transferrin?
Transports iron in the blood and delivers it to the liver and bone marrow for storage.
133
What is the role of ferretin?
Stored intracellular iron.
| Stored within macrophages to prevent free radical formation.
134
What does total iron binding capacity measure?
Meaures the transferrin molecules in the blood.
Typically you want it to be low meaning there isnt a capacitance for more iron.
135
What parasite can cause iron deficiency in the elderly?
Hook worm!
| Think ancylostoma and americanus.
136
What is normocytic anemia?
A stage of iron deficiency where the bone marow is making normal but low levels o RBC.
137
Iron deficiency anemia with an esophageal web and atrophic glossitis.
Pt will present with anemia and dysphagia as well as a BEEFY-RED TONGUE
Pluminer Vinson syndrome.
Treat with supplemental iron.
138
Hepcidin can be produced under what situations?
Can be produced under stages of chronic disease.
Hepcidin sequesters iron in storage sites by limiting iron transfer from macrophages to erythroid precursors and supressing erythopoieten.
139
How does hepcidin sequester free iron under circumstances of infection?
Decrease free iron stores by binding inside macrophages.
And decreases erythroid precursors by supressing erythropoieten.
140
What is sideroblastic anemia?
Anemia due to decreased protoporphyrin synthesis in the liver.
141
Describe the synthesis of protoporphyrin.
Aminolevulinic acid synthetase (ALAS) converse succinyl CoA to aminolevulinic acid (ALA) using vitamin B6!!!!!!!!!
(Rate limiting step)
Aminolevulinic acid dehydrogenase (ALAD) converts ALA to porphobilinogen.
Additional rxns convert porphobilinogen to protoporphyrin.
Ferrochelatase ataches protoporphyrin to iron to make heme.
142
What is necessary in the rate limiting step to form protoporphyrin?
Vitamin B6 is absolutely necessary.
Aminolevulinic acid synthetase converts succinyl CoA to aminolevulinic acid (ALA) using B6 (folate) as a co factor.
Without it you would end up with sideroblastic anemia.
143
Iron laden mitochondria showing iron rings in the mitochondria.
A sign of sideroblastic anemia due to the inability to use iron in the formation of hemoglobin.
144
what are the three aquired forms of sideroblastic anemia?
Alcoholism - Mitochondrial poisoning.
Lead poisoning - Inhibits ALAD and ferrochelatase stopping perphorin synthesis.
```
Vitamin B6 (folate) deficiency Cofactor for ALAS
(isoniazid treatment for tuberculosis can cause this)
```
145
What is thalassemia?
An anemia that is caused by decreased synthesis of the globin chains of hemoglobin.
146
Crew cut appearance of skull on X-ray with hypersegmented neutrophils and macrocytic anemia.
S Thalasmia major
| Extremely severe form of thalassemia.
147
What is the most common cause of Macrocytic anemia?
MCV > 100
| Most commonly due to folate or vitamin B12 deficiency leading to megaloblastic anemia.
148
Why do folate and vitamin B12 deficiencies lead to macrocytic anemia?
They lead to macrocytic/megaloblastic anemia because both are necessary for the formation of pyradines.
Folate circulates as THF and and donates a methyl group to B12. B12 is then able to donate a methyl group to homocystein producing methionine.
149
How does folate and vitamin B12 deficiency affect neutrophils?
Impaired division of granulocytic precursors leads to hypersegmented neutrophils.
150
What dietary food stuffs has folate?
folate can be absoarbed through vegetable and fruits and is taken up in the jejunum.
the body stores are minimal and so deficiencis develop within months.
151
How is vitamin B12 absoarbed in the gut?
Absoarbed by animal derived proteins.
Amylase from saliva liberate vitamin B12 that is then bound to an r binder and carried through teh stomach.
Pancreatic proteases in the duodenum detach B12 from the R binder and it then binds intrinsic factor in the small bowl for reabsorption in the ILEUM.
Vitamin B12 has years of storage in the liver and is less likely to be deficient.
152
What type of anemia will present if there is a lack of B12
Pernicious anemia.
Remember that folate deficiencies will cause megaloblastic anemia.
And that folate and B12 are dependent on eachother for DNA synthesis through the THF/ Homocysteine pathway.
153
In fatty acid synthesis, Vitamin B12 is a cofactor for what mechanism?
Converts methylmalonic acid to succinyl CoA.
Deficiencies wil then lead to increased levels of methylmalonic acid that impairs spinal cord myelinization leading to loss of vibration sense and spastic paresis.
154
Describe how B12 deficiency causes spastic paralysis and loss of vibratory sensation.
Vitamin B12 is used to convert methylmalonic acid to succinyl-CoA in fatty acid synthesis.
thus without it methylmalonic acid builds up in the system and causes nerve damage to the dorsal column and the lateral cortical spinal tract causing spastic paralysis and loss of vibratory sensation.
Note that this is with B12 deficiency, not folate. Makes for good differential.
155
What is extravascular hemolysis?
RBC destruction by the reticuloendothelial system (macrophages of the spleen, liver, and lymph nodes.)
156
What is intravascular hemolysis
RBC within the vessels due to hemoglobinemia, hemoglobinuria and hemosiderinuria.
157
What is hereditary spherocytosis
A type of normocytic anmia with predominant extravascular hemolysis.
Due to inherited defect of RBC cytoskeleton
158
Why do hereditary spherocytosis lead to anemia?
Spherocytes are less able to maneuver through the spleen and macrphages consume them leading to anemia.
treatment is splenectomy to stop the anemia, howell jolly bodies and spherulocytes will continue to exist.
159
What is the amino acid change in sickle cell anemia?
Autosomall recessive switch of glutamic acid with an abnormal valine that is hydrophobic.
HBS polymers aggregate when deoxygenated.
HBF is protective at birth.
160
what effect can hydroxy urea treatment at birth have?
Can increase HbF concentrations in the blood.
161
What are the microscopic changes seen with sickle cell anemia?
Target cells
and
Sickle cells.
162
What is the amino acid swap in hemoglobin C patients?
Normal glutamic acid is replaced by a lysine.
163
what is paroxysmal nocturnal hemoglobinuria?
Aquired defect in myeloid stem cells resulting in absent GP1 (holds decay accelerating factor inhibited) rendering the cell to destruction by compliment.
the hemolysis thn occurs episodically often during sleep at night. Look for intravascular hemolysis.
164
How can one test for paroxysmal nocturnal hemoglobinuria?
Sucrose test
| Confirmatory test is acidifies serum test or flow cytometry to detect the lack of CD55 (DAF) on RBC.
165
What is glucose -6 -phosphate dehydrogenase deficiency?
X linked recessive
Reduced G6PD leads to cells being suceptible to oxidative stress.
Be careful with fava beans in these people.
166
What RBC type will be seen histologically following oxidative stress in G6PD deficient patients?
Heinz bodies.
Primaquine, sulfa drugs, and dapsone can all cause oxidative stress that would be dangerous in these patients.
167
What are heinz bodies?
Cells that have had a bite taken out of them by macrophages in the spleen.
Another name for it is bite cell.
Leads to intravascular hemolysis.
168
Which antibody tends to bind RBC in the heat?
Cold?
IgG in the heat (central body)
IgM in the cold (extremities) Think mycoplasm pneumo.
169
Direct coombs test
detects antibodies bound to a RBC.
| Anti-IgG is added to the patients RBC.
170
Indirect coombs test
Confirms the presence of antibodies in a patients serum.
171
What is microangiopathic hemolytic anemia?
Intravascular hemolysis that occurs as RBC pass through the circulation.
172
If a patient has anemia as well as a low reticulocyte count what should you be considering?
At this point one should be considering the possibility of bone marrow corruption.
Think EPO destruction/kidney damage, bone marrow damage, or microcytic/macrocytic causes
173
What is aplastic anemia?
Damage to the hematopoietic stem cells resulting in pancytopenia
Which is anemia, thrombocytopenia, and leukopenia.
A bone biopsy will reveal fatty empty marrow.
174
What is leukopenia
Below normal WBC count
| <5K
175
What is leukocytosis?
A high WBC count >10K
176
What do myeloblasts produce?
Neutrophils
Basophis
Eosinophils.
177
What type of lymphoma can cause eosinophilia?
Hodgkins lymphoma
178
What type of leukemia can lead to basophilia?
Myeloid leukemia.
179
The monospot test can screen for....
EBV
| Usually positive within 1 week after infection.
180
EBV patients are at risk for forming a rash to what drug?
ampicillin.
181
Describe what markers state a patient has acute lymphoblastic leukemia
Seen most commonly in children and down syndrome.
TdT and DNA polymerase staining can be a sign.
182
Philadelphia chromososme
t9:22 seen most commonly in adults with acute lymphoblastic leukemia.
183
What staining can differentiate acute myeloid leukemia?
Myeloblasts
| Crystal agregates of MPO seen as Auer rods.
184
What happens in chronic lymphocytic leukemia?
Neoplastic proliferation of naive B cells co-expressing CD5 and CD20.
Most common leukemia overall.
185
What will be seen in a blood smear with chronic lymphocytic leukemia?
Increased lymphocytes and smudge cells.
Look for hypogammaglobinemia as well. Most common cause of death in CLL.
186
Hairy cell leikemia
Neoplastic proliferation of mature B cells characterized by hairy cytoplasmic prosses.
Will be positive fo tartate resistant acid phosphatase TRAP.
187
Which type of leukemia will have a dry ta on bone marrow testing?
Hairy cell leukemia.
188
Describe chronic myeloid leukemia
Neoplastic proliferation of mature myeloid cells.
Driven by philadelphia chromosome 9;22
Which generates a BCR-ABL fusion protein with increased tyrosine kinase activity.
189
First line treatment for myeloid leukemia
Imatinib blocking tyrosine kinase activity.
190
What is polycythemia vera?
Neoplastic proliferation of mature myeloid cells especially RBC's
associated with AK2 kinase mutation.
LOOK FOR ITCHING AFTER BATHING.
TREAT WITH PHLEBOTOMY AND SECOND LINE HYDROXYUREA.
191
What is essential thrombocythemia?
Associated with JAK2 kinase mutation
| Neoplastic proliferation of mature myeloid cells especialy platelets.
192
which part of the lymph node tends to enlarge with viral infections?
Paracortex T cell region
193
Which part of the lymph node tends to enlarge with rheumatoid arthritis and early stages of HIV infection?
The follicular region B cell.
194
Describe non-hodgkins lymphoma
Found in 60% of patients with malignant lymphoid cells.
Will arise as painless lymphadenopathy late in adulthood.
195
Describe hodgkins lymphoma
Look for the owl eye reed sternberg cells.
Will find in young adults
196
Which type of lymphoma is heavily associated wth inflammatory states such as hashimoto thyroidits, sjorgren syndrome and H. pylori gastritis?
Marginal zon lymphoma.
Gastric Maltoma is an example.
197
What is Burkitt lymphoma?
Neoplastic proliferation of intermediate sized B cells associated with EBV.
African form usually involves the jaw.
DRIVEN BY C-MYC GENE translocation t8;14 onto chromosome 8
198
Systemic hypertension
140/90 mm Hg
199
what is atherosclerosis
Intimal plaque obstructing blood flow
Nectotic lipid core in large/medium sized arteries.
Starts with fatty streaks early in life and progresses to atherosclerotic plaque.
200
what is arteriosclerosis?
Narrowing of small arterioles
Can be hyaline or hyperplastic types.
Hyaline is with long standing benign hypertension or diabetes.
Hyperplastic arteriosclerosis involvs thickening of vessel wall by hyperplasia of smooth muscle.
201
which part of the aortic wall is dislodged in aortic dissection?
Intimal tear with dissection of blood through the media of the aortic wall.
Think margans synrome and ehlers danlos syndrome.
202
What is a hemangioma?
Benign tumor comprised of blood vessels.
commonly present at birth and regresses during childhood.
203
What is an aniosarcoma?
Malignant proliferation of endothelial cells
Highly agressive.
204
what is kaposi sarcoma
Low grade malignant proliferation of endothelial cells associated with HHV8
205
Stable angina
Chest pain that arises with exertion or emotional stress.
due to atherosclerosis of the coronary arteries > 70%.
Likely ST depression due to subendocardial ischemia.
206
Unstable angina
Chest pain at rest look for ST depressions. and partially occluded coronary artery due to embolism.
Releived by nitro.
207
Prinzmetal angina
ST elevation due to full coronary artery vasospasm leading to transmural ischemia.
Releived by nitro or calcium channel blockers.
208
What is the most sensitive marker for MI?
Troponin I Gold standard
Rise 2-4 hours post and peak at 24 returning to normal by 7-10 days.
CK-MB is best for testing for reinfarcation as levels start over after 72 vhours.
209
What usually causes sudden cardiac death?
Usually due to fatal ventricular arrhythmia.
Mitral valve prolapse, cardiomyopathy and cocaine.
210
Presents with hypertension in the upper extremities and hypotension in the lowerextremities.
Coarcation of the aorta.
Look for notching of the ribs due to engorged intercostal arteries.
Associated with turner syndrome.
211
What is the most common cause of rhinitis?
Inflammation of the nasal mucosa
| Adenovirus is the most common cause.
212
Most common cause of acute epiglottits?
Inflammation most commonly caused by H influenzae type b
213
Most common cause of laryngotracheobronchitis (croup)
Parainfluenza virus.
214
what type of HPV can cause laryngeal papiloma?
HPV6
| HPV 11
215
What is the most common cause of secondary pneumonia superimposed on COPD?
Haemophilus influenzae
216
Most common form of pneumonia in Cystic fibrosis patients?
Pseudomonas
217
Most common cause of atypical pneumoniae in anfants?
Resiratory synctial virus (RSV)
218
Atypical pneumonia with high fever (Q fever) seen in farmers and vetrinarians?
Coxiella burnetti
219
Blue bloaters
Chronic bronchitis with excessive mucus plugs trapping carbon dioxide.
220
Alpha 1 anti trypsin is a rare cause of....
Emphysema
Results in severe panacinar emphysema in the lower lobes.
"Pink Puffer"
221
Pink puffer
Emphysema
222
What type of respiratory disorder is asthma?
Asthma is a obstructive dsorder
Stimulates TH2 cells that secrete IL-4 IgE and IL-5 IgA
223
Bronchiectasis
Permanent dilation of bronchioles and bronchi leading to loss of airway tone and air trapping.
Kartagener syndrome is a defect in dynein arm disrupting ciliary elevator.
224
What is sarcoidoisis?
Systemic disease characterized by noncaseating granulomas in multiple organs CLASSICALLY IN AFRICAN AMERICAN FEMALES.
Leads to a restrictive lung disease.
225
Neonatal respiratory distress syndrome
Seen when the type II pneumocytes arent making enough surfactant.
amniotic fluid lecithin to sphingoyelin ratio used for screening.
226
describe the two most common forms of lung carcinoma
Small cell carcinoma not amendable to resection.
Non small cell carcinoma treated with resection. Can include adenocarcinomas, sqamous cell carcinoma, and large cell carcinoma/carcinoid tumor.
227
Horners syndrome triad
Droopy eyelid - ptosis
Miosis (pinpoint)
Anhidrosis
Due to loss of the sympathetic chain.
228
In a pneumo thorax, the trachea is pushed to which side?
Pushed to the side of the collapse.
229
Difference between oral leukoplakia and a candida infection?
Candida can be scrapd off leukoplakia cannot.
230
What is mallory weissyndrome?
Logitduinal laceration of mucosa at the gastroesophageal junction caused by severe vomitting seen in alcoholism and bulmia.
231
Where does the distal esophageal vein normally drain into?
Drains into the portal vein via the left gastric vein.
Varices can occur when there is portal hypertension.
232
What is aclasia?
Disordered esophageal motility with the inability to relax the lower esophageal sphincter.
Loss of myenteric plxus.
T.Cruzi can cause this.
"Bird beak sign with barium swallow"
233
What is the most common type of cancer that barretts esophagus can become?
Adenocarcinoma.
234
What lymph nodes do esophageal carcinoma spread to when in the upper 1/3 middle 1/3 and lower 1/3
Upper 1/3 is to the cervical nodes
Middle 1/3 is to the mediastinal or tracheobronchial nodes
Lower 1/3 is to the celiac and gastric nodes.
235
Projectile nonbilious vomiting, visible peristalsis and olive like mass in the abdomen.
Pyloric stenosis!
Treatment is myotomy.
236
Most common site for an H. pylori infection?
The antrum.
Look for possible MALT lymphoma.
237
Therapy for H. pyori infections
clarithromycin
omeprazole
ampicillin
238
Duadenal ulcer
Almost always due to H. pylori.
Look for hypertrophy of the brunners glands.
239
Signet ring cells that diffusely infiltrate the gastric wall.
This is a type of gastric carcinoma.
Shows with thickening of the stomach wall.
Can involve the left supraclavicular lymph node (VIRCHOW node)
240
What is virchows node?
Left supraclavicular lymph node.
241
Celiac disease
Immune mediated damage of small bowel villi due to gluten exposure.
gliadin interacts with MHC II mediating cellular damage. Mostly IgA mediated against endomysium.
242
Tropical sprue
Damage to the small bowel villi due to an unknown organism leading to malabsorption.
243
Whipple disease
Systemic tissue damage characterized by macrophages loaded with T. whippeli organisms.
Clasically in the small bowel lamina propria.
244
Abeta lipoproteinemia
Lack B-48 apolipoprotein and thus cannot form chylomicrons.
VLDL and LDL will be absent.
245
Carcinoid tumor.
Malignant tumor that secretes serotonin
5-HIAA serotonin biproduct will be abundant in the urine.
Excess serotonin can cause carcinoid heart disease as well.
246
Inflammatory bowel disease
Chronic relapsing.inflammation of the bowel.
Cassically in young women/
247
Hirschsprung disease
Constant relaxation/peristalsis of the rectum and distal sigmoid colon associated with down syndrome.
Due to congenital failure of ganlion cells to migrate to intestins.
248
Which layers of intestine can the myenteric plexus be located between?
Located between the inner circular and outer longitudina muscle layers.
Gives motility.
249
Where can the submucosal /meissners plexus be located?
Found in the submucosa and regulates bood flow, secretions and absorption.
250
Irritable bowel syndrome
Relapsing abdominal pain with bloating, flatulence, and change in bowel habits.
Related to disturbed intestinal motility. No other identifiable changes.
251
Familial adenomatous polyposis
Autosomal dominant disorder characterized by numerous adenomatous coloninc polyps due to mutated APC gene.
Colon and rectum normally removed prophylacticly.
252
Peutz jeghers syndrome
Hamartomatous polyps in the GI tract and mucocutaneous hyperpigmentation on lips, oral mucosa, genital skin.
253
how does left sided colon carcinoma usually appear
Napkin ring appearance with decreased stool caliber, lower left quadrant pain and bloody stool.
254
How does right sided colonic carcinoma usually appear?
Grows as a raised lesion presenting with iron deficiency and vague pain.
255
Describe TNM stagins
```
T = Depth of the tumor
N = Spread to regional lymph nodes
M = Metastasis distant spread.
```
256
What serum tumor marker is great for assessing treatment response to colonic cancer?
CEA
257
What is annular pancreas?
Developmental malformation in which the pancreas forms around the duodenum.
258
Epigastric abdominal pain that radiates to the back with nausea and vomitting should have you thinking of...?
Pancreatitis.
Look for elevated serum lipase and amylase levels although lipase levels will be more specific.
259
What are the most common causes of chronic pancreatitis in adults and children?
Most commonly due to alcohol in adults
Cystic fibrosis in children.
However it can be idiopathic.
Look for fat soluble vitamin deficiencies.
260
which section of the pancrease does cancer most commonly arise?
Most commonly arise in the head of the pancreas.
261
What is trousseau's sign?
Migratory thrombophlebitis
Presinting with swelling erythema and tenderness in the extremetie.
Common to pancreatic carcinoma.
262
Whipple procedure
Removal of head and neck of pancrease.
Proximal duodenum
Gallbladder.
Used to treat pancreatic carcinoma.
263
What are the most common type of gallstones in the west?
Cholesterol stones.
264
Which liver fluke can cause biliary stones?
Clonorchis sinesis the chinese liver fluke
Treat with praziquantel.
265
Pt presents with exceedingly high levels of unconjugated billirubin that overwhelm the liver and cause jaundice
Begin thinking paravascular hemolysis or ineffective erylhropoieses.
Pt will present with very dark urine.
266
Giberl syndrome
Mildly low UGT activity in the liver leading to unconjugated jaundice during times of stress.
267
Crigler-Najjar syndrome
Absence of liver UGT enzyme leading to inability to conjugate billiruben.
Often fatal.
268
Dubin Johnson syndrome
Deficiency of bilirubin canalicular transport protein leading to a dark liver.
269
Hepatitis D depends on what for infection?
Hepatitis B infection to allow for a super infection.
270
In hepatitis B infections, what is the first serologic marker to ris?
HBsAG
271
In a chronic hepatitis B infection, what antigens/antibodies wil be present?
HBeAg indicates infectivity.
IgG should be present.
272
What is the most common cause of liver disease in the west?
Alcohol.
Will progress from a fatty liver to alcoholic hepatitis to cirrhosis.
Acelaldehyde (metabolite of alcohol mediates the damage). Leads to hepatic swelling and formation of mallory bodies.
AST > ALT for alcohol damage
ALT > AST for viral damage.
273
How could one differntiate fatty liver in obesity vs alcoholism?
ALT will be elevated in obesity
AST will be elevated in alcoholism.
274
What is the classic triad of hemochromatosis?
Cirrhosis
Secondary diabetes mellitus
Bronzing of the skin.
Use prussian blue stainin to look for lipofuscin and iron deposits.
275
Wilsons disease
Lack of copper transport into the bile.
Copper builds up in the hepatocytes leaks into the serum and deposits into tissues.
Cause Kayser-Fleisher rings in the cornea.
276
Reyes syndrome
Fulminan liver failure and encephalopathy in children with viral illness who take aspirin.
Likely mitochondrial damage of hepatocytes.
277
What structure does the horseshoe kidney wrap itself around?
Abnormally wrapped around the inferior mesenteric artery root as it descends from the pelvis to the abdomen.
278
Renal angenesis
Absent kidney formation
279
Polycystic kidney disease
Inhrited defect leads to bilaterally enlarged kidneys with cysts in the renal cortex and medulla.
280
Prerenal azotemia
Decreased blood flow to the kidneys.
Look for BUN elevation
281
Postrenal azotemia
Obstruction of urinary tract in ureters decreases GFR.
During early stages, BUN elevates in the blood and tubular function remains intact.
With long standing obstruction tubular damage occurs and sodium reabsorption/ ability to concentrate urine greatly decreases.
Urine osmolarity < 500 m OSM
282
Acute tubular necrosis
Injury and necrosis of the tubular epithelial cels.
look for necrotic cells plugging tubules decreasing GFR and causing brown casts to be seen in the urine.
283
What are the most common nephrotoxic agents?
Aminoglycosides
Heavy metals
Myoglobinuria.
284
Acture interstitial nephritis
Drug induced hypersensitivity involving the intersititium of the tubules.
Results in acute renal failure.
285
Renal papillary necrosis
Necrosis of the papillae
Caused by analgesic abuse long term phenacetin or aspirin use.
Diabetes
Sickle cell
Severe or acute pyelonephritis.
