6/12 UWorld Flashcards
1
Q
What is responsible for the activation of kallikrein
A
Factor XIIa converts prekallikrein to kallikrein
2
Q
Describe the kinin pathway
A
- Factor XIIa converts prekalikrein to kallikrein
- Functions of Kallikrein:
- Kallikrein cleaves plasminogen to plasmin
- Plasmin breaks down the fibrin mesh
- So factor XIIa is a regulator to make sure the coagulation cascade doesn’t go too crazy
- Kallikrein converts high molecular weight kininogen (HMWK) to bradykinin
- Bradykinin has 3 functions:
- Vasodilation
- Increased vascular permeability
- Pain mediator
- This is why coagulation and inflammation are interconnected
- Bradykinin has 3 functions:
- ACE is responsible for degrading bradykinin
- So bradykinin can cause angioedema in patients taking ACEI
- Kallikrein cleaves plasminogen to plasmin
3
Q
What is the MOA of Heparin
A
Binding and activation of Anti-thrombin III, so that there is inactivation of thrombin (II) and factor X
4
Q
Describe the pathophysiology behind Heparin-induced thrombocytopenia
A
- Heparin binds to platelet factor 4
- Antibodies form against this complex
- Antibody-heparin-PF4 complex can then destroy platelets, and their fragments will activate remaining platelets
- Leads to thrombocytopenia and hypercoagulable state
5
Q
What is the difference between Unfractionated heparin and LMWH
A
LMWH only increases inhibtion of Factor X, not thrombin (II)
LMWH effects are not inhibited by protamine sulfate
LMWH has greater bioavailability and longer half life
Does not require PTT monitoring
6
Q
What type of drugs are:
- BivaliRUDIN à No IntRUDIN sign
- ArGATROban à big gators
- DabiGATRAN à big gators
What are they used for
A
Direct thrombin inhibitors
Used for treating Heparin-induced thrombocytopenia
7
Q
What is the mechanism behind Warfarin-induced skin necrosis
A
Due to early hyper-coagulable state due to depletion of protein C and S
8
Q
What is the first and last Vitamin K-dependent factor to be reduced
A
Factor VII is the first to be reduced
Factor II has the longest half life
9
Q
What molecule is responsible for biconcavity of RBC
A
Spectrin
10
Q
MOA of fibrinolytics
A
Activate the conversion of plasminogen to plasmin
11
Q
What are acanthocytes (“spur cells”) and what diseases are they seen in
A
- “Spur cells” - cells with irregular spikes (vs. echinocytes)
- Seen in states of cholesterol dysregulation:
- liver disease, abetalipoproteinemia
12
Q
What are echinocytes (“burr cells”) and what disease are they seen in?
A
RBCs
“Burr cells” – uniform projections (vs. Acanthocytes)
Seen in renal failure
13
Q
Causes of target cells
A
- HbC disease
- Asplenia
- Liver disease
- Thalassemia
14
Q
What are Howell Jolly bodies and what causes them?
A
- Basophilic nuclear remnants found in RBCs
- Can only be one in each RBC because there can only be one nucleus
- Seen in patients with hyposplenia or asplenia
15
Q
What will cause resistance to Heparin in patients
A
Anti-thrombin deficiency
16
Q
Where does erythropoeisis occur in early life and later life
A
- Fetal development - liver
- After 28 weeks - bone marrow Infancy and childhood:
- Flat bones
- Sternum, pelvis, ribs, cranial bones, vertebrae, long bones of leg
- Later adolescence and adulthood
- Axial skeleton
- Vertebrae, sternum, ribs, and pelvis
17
Q
Tumors that secrete erythropoeitin
A
- Potentially Really High Hematocrit
- Pheochromocytoma
- Renal cell carcinoma
- Hepatocellular carcinoma
- Hemangioblastoma
18
Q
Presentation of acute intermittent porphyria
A
5 P’s: Painful abdomen, Port wine colored urine (due to increase PGB), Polyneuropathy, Psychological disturbances, Precipitated by drugs (CYP450 inducers), alcohol, and starvation
19
Q
What is the deficient enzyme in porphyria cutanea tarda
A
Uroporphyrinogen decarboxylase
(THINK of a stereotypical homeless man living in a cardboard box)
Cardboard box = carbox = carboxylase
Alcholics pee on themselves = “You peed” = UP = uroporphyrinogen
20
Q
Enzyme deficiency and presentation of lead poisoning
A
- Inhibition of ALA dehydratase or Ferrochelatase
- Leading to microcytic anemia
- Presentation:
- GI (abd pain, constipation, anorexia)
- Neuro (cognitive defects, peripheral neuropathy, encephalopathy, memory loss, delirium)
- Hematologic (microcytic anemia with basophilic stippling, ringed sideroblasts in marrow)
- Burton lines – lead lines in gingiva and gums
- Hyper dense lines on metaphysis of long bones
- Renal failure
21
Q
Describe the defect and presentation of orotic aciduria
A
- Inability to convert orotic acid to UMP (de novo pyrimidine synthesis) due to defective UMP synthase
- Presentation:
- Failure to thrive
- Developmental delay
- Megaloblastic anemia refractory to folate and B12
- No hyperammonemia
- Vs. Ornithine transcarbamylase deficiency which has increased orotic acid + hyperammonemia but no megaloblastic anemia
- No hyperammonemia
22
Q
Describe beta thalaseemia major (genes, presentation, histology)
A
- No B-globin at all
- Severe anemia requiring blood transfusions
- Risk of hemochromatosis
- High HbF at birth is temporarily protective
- Will see target cells
- Erythroid hyperplasia – hematopoiesis occurring in unusual places, such as face, skull, liver, spleen
- “Crewcut” appearance on X-ray (“hair-on-end”)
- “Chipmunk” facies
- Hepatosplenomegaly
- Risk of aplastic crisis with Parvovirus B19 infection of erythroid precursors
23
Q
What are the disorders that cause
- Erythroid hyperplasia – hematopoiesis occurring in unusual places, such as face, skull, liver, spleen
- “Crewcut” appearance on X-ray (“hair-on-end”)
- “Chipmunk” facies
- Hepatosplenomegaly
A
Beta-thalassemia major
Sickle cell disease
24
Q
Treatment of sickle cell anemia
A
- Hydroxyurea – increases production of HbF
- Bone marrow transplant
25
What is the protein that carries Hb to spleen in intravascular hemolysis
Haptoglobin
Will be decreased in intravascular hemolysis
26
Diagnosis of Paroxysmal nocturnal hemoglobinuria
Ham’s test – add acid to lower the pH and check for RBC lysis
* (a) Paroxysmal nocturnal hemoglobinuria
* Deficiency of GPI, which usually anchors DAF (CD55) to RBC membrane to protect from complement destruction
* Complement is activated in acidic situations
* Lysis occurs at night due mild respiratory acidosis
27
Causes of macrocytic anemia
* Megaloblastic anemia
* Folate deficiency
* B12 deficiency
* Orotic aciduria
* Alcoholism
* Liver disease
* Drugs
28
Describe the presentation and histology of aplastic anemia
* Bone marrow stops making cells – pancytopenia
* Anemia
* Fatigue, malaise, pallor
* Decreased reticulocyte count but increased EPO
* Leukopenia
* Infection
* Thrombocytopenia
* Purpura, petechiae, bleeding
* Histology will show hypocellular bone marrow with fatty infiltration (“cobweb”)
29
Describe how ethylene glycol (anti-freeze) affects the kidney
* It is absorbed from the GI tract and metabolized into glycolic acid (toxic to renal tubules – acute tubular necrosis) and oxalic acid (calcium oxalate crystals)
30
Describe pathogenesis and presentation of mitochondrial myopathies
o Maternal inheritance only from mitochondrial DNA
o Pathogenesis:
§ Without properly functioning mitochondria, cells cannot use oxidative phosphorylation to produce ATP
§ Brain and skeletal muscle will be affected first due to high metabolic demand
o Presentation:
§ Myopathy (muscle weakness, myalgia)
§ Lactic acidosis (due to impaired aerobic glycolysis)
§ Nervous system dysfunction (neuropathy, seizures)
§ \*\*\*Muscle biopsy shows ragged red fibers (due to accumulation of diseased mitochondria)
31
Describe how the enzymes transcribed by IFN-a and IFN-b to halt protein transcription only work on infected cells and not uninfected cells
These enzymes are only active in the presence of double stranded RNA, which forms in infected cells as a result of viral replication
So normal protein synthesis can still occur in uninfected cells and is selectively inhibited in virally infected cells
32
MOA of fibrates
* Decreases serum VLDL (35-50% and decreased triglycerides by activating PPAR-alpha at liver and peripheral tissues
* = news PPAR of light house attendant, being used as a signal
* When activated, PPAR-alpha upregulates LPL at extra-hepatic sites
* This means increased hydrolysis of chylomicron and VLDL TG’s at peripheral tissues – aka decreased serum TGs
* = Jellyfish taking down VLDL ship
* = trident passengers escaping from ships that were trapped by jellyfish
* Less VLDLs means less conversion into LDLs (very mild effect )
* = jelly fish sinking LDL ship
* Elevate HDLs
* Fibrates activate the synthesis of Apolipoproteins A1 and A2 by hepatocytes, which are necessary for production of nascent HDLs
33
What are the 4 M's associated with the rule of 4
1. Motor pathway - contralateral weakness
2. Medial lemniscus - contralateral proprioception/vibration
3. MLF - ipsilateral internuclear ophthalmoplegia
4. Motor nerve nucleus - ipsilateral CN motor/midline loss (3, 4, 6, 12)
34
What are the 4 S's associated with Rule of 4
1. Spinocerebellar - ipsilateral ataxia (finger to nose)
2. Spinothalamic - contralateral pain and temp
3. Sensory CN V - ipsilateral pain and temp of face
4. Sympathetic - ipsilateral Horner syndrome
35
What is a common cause of isolated systolic HTN
Age-related increased arterial stiffening leading to decreased compliance of aorta and other major arteries
36
What apolipoprotein increases risk for Alzheimers and which decreases risk
* ApoE2 is protective
* ApoE4 has increased risk (due to increased production of beta-form of APP)
THINK: when you have only 2 kids you can protect them, when you have 4 kids there is increased risk because you are distracted
37
What CNS tumor do you see a fried egg appearance
Oligodendroglioma
38
Treatment for exophthalmos in Graves
Glucocorticoids
Recall that exophthalmos is due to inflammatory infiltrate
* Lymphocytes infiltrate the orbital tissues and secrete cytokines that stimulate fibroblasts to secrete increasing amounts of glycosaminoglycan ground substance such as hyaluronic acid. This increased hyaluronic acid draws water into the orbit resulting in extraocular muscle edema. Combined with interstitial edema, this process pushes the globe outward (proptosis). A sensation of grittiness and excessive tearing occur because the lids are now unable to completely cover the proptotic globe. Desiccation and keratitis may result
39
Differentiate between CSF in bacterial vs. viral meningitis (glucose, protein, WBC)
* Viral:
* No organisms on gram stain and culture
* Protein \< 150 (less elevated than in bacterial)
* Glucose normal or slightly slow
* Lymphocytic predominance
* WBC \< 500
* Bacterial:
* Gram stain positive
* Protein \> 250
* Glucose \< 46
* Neutrophlic predominance
* WBC \> 1000
40
What characteristic of viruses allows them to undergo rapid genetic shift?
Segmentation
antigenic segments of RNA are shared to form a new species
41
What are the segmented viruses?
* There are 4 segmented viruses = BOAR
* Bunyavirus (3 segments)
* Orthomyxo (8 segments)
* Arenavirus (2 segments)
* Rheovirus (11 segments)
42
What causes antigenic drift
Point mutations in the viral genome leading to changes in the hemagglutinin (HA) and neuraminidase (NA) molecules
43
What part of the catecholamine synthesis pathway is affected by cortisol?
Norepinephrine to Epinephrine via Phenylethanolamine-N-methyltransferase (PNMT)
* Epinephrine is predominantly produced in the adrenal medulla
* Expression of Phenylethanolamine-N-methyltransferase (PNMT) in the adrenal medulla is upregulated by cortisol
* Production of epinephrine can be decreased by pituitary resection because decreased ACTH = decreased cortisol = decreased PNMT
44
How does pregnancy effect levels of thyroid hormone
Pregnancy cause increased thryoxine-binding globulin (TBG) --\> high total thyroid hormone levels but low free hormone
Patient will be euthyroid with normal TSH
