DIT-Things to know 2 Flashcards
MEN1
Parathyroid adenoma Pituitary adenoma Pancreatic tumor - Gastrinoma - Insulinoma (hypoglycemia) - Glucagonoma (hyperglycemia and diabetes) - VIPoma (diarrhea)
MEN2A
Medullary thyroid cancer
Pheochromocytomas
Parathyroid hyperplasia
RET oncogene
MEN2B
Medullary thyroid cancer
Pheochromocytoma
Mucosal neuromas
RET oncogene
What might a lab detect in the urine or plasma of a patient with pheochromocytoma?
Plasma
- Metanephrine
- Normetanephrine
Urine
- Vanillylmandelic acid (VMA)
Most common tumor the adrenal gland
Most common tumor of the adrenal medulla (in adults)
Most common tumor of the adrenal medulla (in children)
Medical treatment for pheochromocytoma
Pheochromocytoma, medullary thyroid cancer, hyperparathyroidism
Pheochromocytoma, medullary thyroid cancer, mucosal neuromas
- Benign, non-functioning adrenal adenoma
- Pheochromocytoma
- Neuroblastoma
- Non-selective alpha blocker
- MEN2A
- MEN2B
Which cell wall inhibitor matches each of the following?
- Next step in tx of otitis media if amoxicillin resistant
- Prophylaxis against bacterial endocarditis
- Sufficient for the treatment of syphilis
- Single-dose treatment for gonorrhea
- Amoxicillin + Clavulonic avid
- Penicillin V, Aminopenicillins, 1st gen cepahlosporins
- Penicillin G
- Ceftriaxone
Equation for confidence interval
CI= mean +- Z (SEM)
Stages of grief
Denial Anger Bargaining Grief Acceptance
In what gestational week does they thyroid begin to develop?
Embryonic origin?
Third week of gestation
Derived from endoderm from the floor of the primitive pharynx
Remnants of thyroid development
Thyroglossal duct
- connection from tongue to thyroid
- infection risk
Foreamen cecum
- more common
- middle of tongue
What is the most common site of ectopic thyroid tissue?
Tongue
Hypothyroidism will cause elevation in what labs?
LDL and Total cholesterol
Formation of thyroid hormone
- Na gradient brings Iodide (I-) into follicle
- Iodide is oxidized by Peroxidase to iodine (I2)
- Organification= Iodine binds to thyroglobulin (Tg)
- Thyroid hormone is formed inside they thyroglobulin by union of tyrosine and iodine
- Coupling or condensation of MIT and DIT –> T3 and T4
What converts T4 –> T3 in periphery
Propylthiouracil
Labs seen in Hypothyroidism
Increased TSH
Decreased T3 T4
Baby with impaired growth
Intellectual disability
Enlarged tongue
Distended abdomen
What could of fixed this
Iodine to mother during development
Hashimoto thyroiditis
- type of rxn
- infiltrate
- genes
- increased risk of
Type IV hypersensitivity
Lymphocytic infiltrate
HLA-DR5 and HLA-B5
Risk: B cell lymphoma of thyroid
Painful Goiter
- infiltration
- triggered by
- Tx
Subacute (granulomatous, de Quervain) thyroiditis
Granulomatous infiltration
Viral infection
- Coxsackievirus
- Echovirus
- Adenovirus
- Measles
- Mumps
NSAIDS
Corticosteroids
Fixed, hard painless goiter
- tissue
- infiltrate
- may see
Riedel’s thyroiditis
Chronic inflammation of thyroid –> replaced by fibrous tissue
Hypothyroid
Euthyroid
Macrophages and eosinophils
Extension of fibrosis into local structures (airway)
Pregnancy affect on serum thyroid hormone levels
Pregnancy = increased estrogen
Estrogen increases thyroid binding globulin (TBG)
Binds up circulating thyroid hormone, thyroid senses T3/T4 dropping so releases more
Total T3/T4 increased
Free T3/T4 normal
Hyperthyroidism vs thyrotoxicosis
Hyperthyroidism: thyroid is making too much thyroid hormone
Thyrotoxicosis: too much thyroid hormone from any reason
- Exogenous hormone
- Thyroid inflammation
Graves disease MOA
- Associated with
- key features
- Tx
Autoimmune
TSI binds to the TSH receptor and stimulates the thyroid gland to secrete T3 and T4
HLA-DR3 and HLA-B8
Exophthalmos
Pretibial myxedema
- Abnormal connective tissue deposit in orbit, extraocular muscle or skin on front of shins
Methimazole (preferred)
Propylthiouracil (PTU)
Beta blocker (tachycardia and anxiety)
Benign tumor that can present with hyperthyroidism
Struma ovarii teratoma
Contains functional thyroid tissue
Most likely diagnosis of patient with hyperthyroidism?
- Extremely tender thyroid gland
- Pretibial myxedema
- Pride in recent weight loss, medical professional
- Palpation of single thyroid nodule
- Palpation of multiple thyroid nodules
- Recent study using IV contrast (iodine)
- Eye changes: proptosis, edema, injection
- History of thyroidectomy or radioablation of thyroid
- Subacute (de Quervain) thyroiditis
- Graves disease
- Thyroid hormone abuse
- Toxic thyroid adenoma
- Multinodular goiter
- Jed0Basedow phenomen
- Graves disease
- Too much exogenous thyroid hormone
A Tall thin male teenager has abrupt onset of dyspnea and left-sided chest pain. Percussion on the affected side reveals hyper-resonance, and breath sounds are diminished. What is most likely?
Spontaneous pneumothorax
Attributable risk
(A/ A+B) - (C/ C+D)
Ground glass appearance of cytoplasm of thyroid
Papillary thyroid cancer
Orphan annie eyes
Papillary thyroid cancer
Concentric calcification
Psammoma bodies
Papillary thyroid cancer
Mutation of papillary thyroid cancer
RET gene mutation
BRAF
Uniform cuboidal cells lining follicles and invading capsule
- spread
- associated with
Follicular thyroid carcinoma
Hematogenously
RAS mutation
PAX8-PPAR gamma 1 rearrangment
Tumor of thyroid
Increased level of calcitonin
Associated with
Mutation
Medullay thyroid carcinoma
Proliferation of parafollicular C cells
RET gene mutation
MEN 2A and MEN2B
Tumors that activate tyrosine kinase receptor
Follicular thyroid carcinoma
Medullary thyroid carcinoma
Rock hard thyroid with local extensions
Elderly patient
Anaplastic thyroid carcinoma
Undifferentiated
Rapidly fatal
What type of cancer in thyroid?
1) Arises from parafollicular C cells
2) RAS mutation or a PAX8-PPARy-1 rearrangment
3) Rearrangement in RET oncogene
4) Mutation in BRAF gene
5) Enlarged thyroid cells with ground-glass nuclei
1) Medullary thyroid carcinoma
2) Follicular thyroid carcinoma
3) Medullary thyroid carcinoma, papillary carcinoma
4) Papillary carcinoma
5) Papillary thyroid cancer
What nerve can be damaged in thyroid surgery
Result?
Recurrent laryngeal n.
Hoarseness
Number needed to harm
1/ AR
AR= (A/A+B) - (C/C+D)
Cell types and secretion in pancreas
Alpha= Glucagon
Beta= Insulin
Delta= somatostatin
Glucagon does what
Stimulates
- Gluconeogenesis
- Glycogenolysis
- Lipolysis (break down of fat adn TG to produce ketones)
- Insulin secretion
GLUT-2
GLUT-4
GLUT-1
GLUT-2 (independent)
- beta cells
- Liver
- Small intestine
- Renal cells
GLUT-4 (Insulin dependent)
- Adipose tissue
- Skeletal muscle
GLUT-1 (independent)
- Brain and RBCs
What glut transport is dependent on insulin
GLUT-4
- Adipose tissue
- Skeletal muscle
Insulin binds to what of fat and muscle cells
Does what
Tyrosine kinase receptor
Causes cell to insert more GLUT-4 transporters into membrane
Type 1 DM
- Ab against
- Association
Islet cell antibody against glutamic acid decarboxylase (GAD)
HLA-DR3-DQ2
HLA- DR4- DQ8
Hemoglobin A1C
Moiety on hemoglobin molecule as it floats around, glucose sticks to it in an non-enzymatic reaction called glycation
More glucose in blood the more it sticks to hemoglobin
Measure percentage of surface area covered in glucose= A1C
Kimmelstiel wilson nodules
Acellular nodules in glomerulus
Diabetes
Too much glucose causes what complications
Leaky vessels
Retinopathy –> hemorrhage –> blindness
Nephropathy –> progressive proteinuria
Vascular disease –> astherosclerosis
Alcohol sugar
Alcohol form of glucose
Glucose –> (this alcohol sugar)
Sorbitol
Aldose reductase
Sorbital –> Fructose
Sorbitol dehydrogenase
Increased glucose –> sorbitol effect on tissues
Some tissues dont have srbitol dehydrogenase
Trapped in cells
- Schwann cells
- Lens
- retina
- kidney
Causes osmotic pressure that draws in free water causes swelling and damage to cell
Motor neuropathy
Sensory neuropathy
Autonomic neuropathy
How is hemoglobin glycosylated in DM to form HgbA1C
Nonenzymatic glycation
Diabetes with a strong genetic predisposition
Type II DM
Polymyositis vs Polymyalgia rheumatica
Polymyositis
- Muscle weakness
- Elevated Ck and aldolase
- ANA
- Anti-Jo 1
Polymyalgia rheumatica
- Joint pain
- Normal Ck and aldolase
- No muscle pain or weakness
Diabetic ketoacidosis
- values
- complications
Hyperglycemia > 150 Hyperkalemia - Excess H, pull H out of cell in exchange for K - Dump K in urine -Total K low
Arrhythmias
- serum hyperkalemia, total body potassium depletion
V tach
Torsades
Invasive fungal infections
- Mucormycosis (brain abscess)
Extreme hyperglycemia > 800
Hyperosmolar Hyperglycemic state
Type II DM
How do acidosis and alkalosis affect extracellular K concentrations?
Acidosis
- Increases extracellular K concentration
- Pushes H into cells
Alkalosis
- Decreases extracellular K concentration
What is Budd-Chiari syndrome
Occlusion of IVC or hepatic veins –> hepatic congestion
Which ECG leads will show evidence of ischemia in an inferior wall MI?
II, III, aVF
What are the findings of Brown-Sequard syndrome
Hemisection of spinal cord
Ipsilateral UMN signs below lesion (lateral corticospinal tract)
Ipsilateral loss of proprioception, vibration sense, and fine touch below lesion
(dorsal columns)
Contralateral loss or pain and temperature sensation 2-3 segments below lesion
(lateral spinothalamic tract)
What produces hromone leptin
Adipocytes
Hypothalamic nuclei that regulate hunger
- Paraventricular nucleus
- Dorsal medial nuclei
- Arcuate nucleus
- Lateral hypothalamus
- Stimulated –> hunger
- Inhibted by leptin
- Lesion –> anorexia - Ventromedial nuclei
- Stimulated by leptin
Lateral likes lunch but lesion (or leptin) lateral you get little
Ventromedial nuclei –> go medially or thinner
Leptin makes you thin
Lipodystrophy
Caused by
Distortions in the structure or function of adipose tissue
Buffalo hump
Leptin deficiency
HIV medication
- Protease inhibitors
5 categories of criteria for the diagnosis of metabolic syndrome
Abdominal obesity Elevated triglycerides Low HDL Elevated BP Elevated glucose
Liver disease associated with obesity
Nonalcoholic steatohepatitis (NASH)
BMI to be obese
> = 30
Substances known for causing methemoglobinemia
Nitrates
Antimalarial drugs
- Chloroquine
- Primaquine
Dapsone
Local anesthetics
- Lidocaine
Sulfonamides
Metoclopramide
Parathyroid gland cells
Chief cells: PTH
Oxyphil cells
- packed with mitochondria
- appear at pubery
- increase with age
Parathyroid innervation
Cervical sympathetic ganglia
Doesnt directly innervated parathyroid
Controls blood flow to parathyroid gland
PTH on bone cells
Increase bone turn over
Ramps up osteoclasts
Osteoclasts: dont have PTH recpetors
Osteoblasts: have PTH receptor
- make cytokine RANKL –> activates osteoclasts
Subperiosteal bone reabsorption on radial aspect of medial phalanges
Tapering of distal clavicles
Salt and pepper appearance skull
Also see?
Osteitis Fibrosis Cystica
Brown tumors of long bones
Primary hyperparathyroidism
Secondary hyperparathyroidism from renal failure values
Increased BUN and Cr
Increased Phosphate
Values for secondary hyperparathyroidism from Vit D deficiency
Increased PTH
Decrased Ca
Decreased or normal phosphate
Decreased Vit D
Pseudohypoparathyroidism
Mutations in gene called GNAS-1
Encodes G protein at PTH receptor in kidney
Increase PTH
Decrease Ca
AD
Albright hereditary osteodystrophy
- Short stature
- Obesity
- Undevelopment of 4th and 5th digits
- Ostitis fibrosa cystica
WAGR complex
Wilms tumor
Aniridia (no iris)
Genitourinary malformation
Retardation (mental and motor)
WT1 deletion
Extrinsic coagulation pathway
Tissue factor pathway
VII
X
Intrinsci coagulation pathway
Contact activation pathway
XII
XI
IX
X
Deficient in factor IX
Hemophilia B
Deficient in Factor VIII
hemophilia A
Accelerating factors for coagulation pathways
Factor V
Factor VIII
What inhibits the accelerating factors for the coagulation pathways
Protein C
Protein S
RL step of coagulation pathway
Factor X
Common Final pathway in coagulation
Factor X –> Xa
Xa + Va activate prothrombin
Thrombin cleaves fibrinogen –> fibrin
Fibrin + XIIIa –> mesh
Warfarin inhibits
Factor II (thrombin) Factor VII (extrinsic) Factor IX (intrinsic) Factor X Protein C Protein S
First seen with starting Warfarin
Inhibit Protein C and Protein S
Transient hyeprcoagulable state
What cleaves Fibrinogen to fibrin
Thrombin (Factor II)
Coagulase from S. Aureus
What is essential for coagulation cascade
Calcium
Factor XI
Kallikrein
Activates plasminogen –> plasmin
Produces Bradykinin
Plasmin
Breaks down fibrin mesh
Prothrombin time (PT)
Add tissue factor and see how long for clot to form
Test
- Tissue factor pathway
- Final common pathway
Factor VII
Factor X
Factor V
Factor II (prothrombin)
Resported with INR
Partial thromboplastin time (PTT)
25-40 seconds
Taking plasma add material to activate contact activation pathway
Factor XII Factor XI Factor IX Factor VIII Factor X Factor V Factor II (prothrombin)
Hemophilia A and B
- deficiency
- increases
Hemophilia A
- Factor VIII deficiency
Hemophila B
- Factor IX deficiency
Increase PTT
Coagulation disorders vs platelet disorders cause what type of bleeding
Coagulation disorders
- macrohemorrhages
Platelet disorders
- Microhemorrhages
Vit K deficiency
Cofactor for several clotting factors
Factor II, VII, IX, X, C and S
diSCo started in 1972
Increase PT and PTT
Factor V Leiden
Hypercoagulable
Makes factor Va resistant to inactivation by protein C
Stays active longer –> more coagulation
Prothrombin G20210A mutation
Hypercoagulable
Predisposes to thrombosis
Mutation Guanine –> Adenine at 20210
Antithrombin deficiency
- resistant to
Hypercoagulable
Unable to inactivate thrombin
Resistant to heparin
Protein C deficiency
Hypercoagulable
Unable to inactivate factor V and VIII
or deficiency in protein S
Which glomerular disease should be suspected most in patients with each of the following findings?
- IF: granular pattern of immune complex deposition; LM; diffuse capillary thickening
- IF: granular pattern of immune complex deposition; LM: hypercellular
- IF: linear pattern of immune complex deposition
- EM: subendothelial humps and “tram track” appearance
- Nephritis, deafness, cataracts
- LM: crescent formation in the glomeruli
- LM: segmetnal sclerosis and hyalinosis
- EM spiking on the GBM due to electron-dense subepthelial deposits
- Membranous GN
Diffuse proliferative GN - Acute post-streptococcal GN
- Goodpasture syndrome
- Membranoproliferative GN
- Alport syndrome
- Rapidly progressive GN
- Focal segmental glomerulosclerossi
- Membranous GN
Heparin induced thrombocytopenia
- What happens
- symptoms
- Tx
Platelet drop
Heparin binds platelet factor 4 –> autoantibody-heparin PF4 complex –> activates platelets
Thrombocytopenia
Hypercoagulable state
Stop heparin
Start direct thrombin inhibitor until platelets back up
Start warfarin
What lab test is used to monitor adequate anticoagulation in a patient taking heparin?
PTT
What lab test is used to monitor adequate anticoagulation in a patient taking warfarin
PT (INR)
Which genetic syndrome is caused by?
- Absence of HGPRTase
- Deficiency of aldolase B
- Deficiency of cystathionine synthase
- Galactose-1- phosphate uridyl transferase deficiency –> intellectual disability, hepatosplenomegaly, cataracts
- Deficiency of tyrosinase
- Lesch-Nyhan
- Fructose intolerance
- Homocystinuria
- Galactosemia
- Albinism
What gives RBC their shape
Average life span RBC
Spectrin
120 days
Anisocytosis
Poikilocytosis
Polycythemia
Erythrocytosis
Reticulocytes
Anisocytosis: RBCs of varying sizes
Poikilocytosis: RBCs of varying shapes
Polycythemia: too many RBCs
Erythrocytosis: too many RBCs
Reticulocytes: immature RBCs
Basophilic stippling
Lead poisoning
RBC with uniform spikes all over surface
Burr cell
Echinocyte
Uremia
Renal failure
Pyruvate kinase deficiency
RBC with irregular spikes in size and distribution
Spur cell
Acanthocyte
Abetalipoproteinemia
Spherical RBCs
Spherocytes
Hereditary sphenocytosis
Fragmented RBCs
Schistocytes
DIC
TTP, HUS
RBCs looks like bulls eye
Target cells
“HALT” said the hunter to his target
Hemoglobin C disease
Asplenia
Liver disease
Thalassemia
Cell type seen in abetalipoproteinemia
Spur cell
Acanthocytes
RBC with irregular spikes in size and distribution
Crescent shaped RBC
Sickle cell
Sickle cell anemia
RBC with basophilic remnant of a nucleus (purple spot in RBC)
Howell-Jolly body
Asplenia
RBC with white spot of oxidized hemoglobin
Heinz body
G6PD
RBC with little part taken out of it
Bite cell
Heinz body removed
G6PD
Tear drop RBCs
Myelofibrosis
Pencil or cigar shaped cells
Elliptocytes
Hereditary elliptocytosis
RBC covered in blue dots
Ringed Sideroblast
Granules of iron
Disorders of heme synthesis
Found in bone marrow
Cell type seen with?
- Lead poisoning
- G6PD deficiency
- DIC
4 Abetalipoproteinemia
- Asplenia
- Basophilic stippling
- Heinz body, Bite cells
- Schistocytes
- Spur cells (acantholysis)
- Howell-Jolly bodies, target cells
Types of Hemoglobin
- HbA
- HbA1c
- HbF
- HbS
- HbC
- Hb Bart’s
- HbH
- Normal
(2 alpha 2 beta) - Poorly controlled diabetes
( 2 alpha 2 beta-glucose) - Fetal hemoglobin
( 2 alpha 2 gamma) - Sickle cell hemoglobin
( 2 alpha 2betaS glu –> val) - Hemoglobin C dis
(2 alpha 2 betaC glu –> lys) - Severe alpha thalassemia
(4 gamma) - Severe alpha thalassemia
(4 beta)
RBC production locations
“Young Liver Synthesizes Blood”
Yolk sac
Liver
Spleen
Bone marrow
An 18-year-old woman presents to the emergency department with acute onset of severe abdominal pain. She says she had a similar attack 1 year earlier after taking some barbiturates.
At that time she underwent an exploratory laparotomy, which revealed nothing. The
patient no longer takes barbiturates but recently
started an extremely low-carbohydrate and low-calorie diet. She has a temperature of
37°C (98.6°F), a respiratory rate of 16/min, and a blood pressure of 128/83 mm Hg. Her
WBC count is normal. Laboratory studies reveal a sodium level of 127 mEq/L, and urinalysis
shows increased porphobilinogen levels.
The physician tells the patient that she has a genetic condition involving her RBCs. What
congenital disorder did the physician most likely tell the patient she has?
(A) Acute intermittent porphyria
(B) Fanconi’s anemia
(C) Hereditary spherocytosis
(D) Porphyria cutanea tarda
(E) Sickle cell disease
A. Acute intermittent porphyria
A 17-year-old boy presents to the emergency department with severe abdominal pain. Laboratory tests show a deficit in uroporphyrinogen synthetase and excess δ-aminolevulinate and porphobilinogen in the urine. Which of the following symptoms would most likely also be present in this patient? (A) Chest pain (B) Hypotension (C) Neuropsychiatric disturbances (D) Polyphagia (E) Stiff neck
C. Neuropsychiatric disturbances
Acute intermittent porphyria
Dark red urine
Psychologic disturbances
Polyneuropathy
Abdominal pain
- deficiency
- drug that precipitated
Treatment
Acute intermittent porphyria
Uroporphyrinogen-1 synthase
(porphobilinogen deaminase)
Precipitated by
- Barbiturates
- Seizure durgs
- rifampin
- metoclopramide
Give Heme and Glucose
- down regulates delta-ALA synthase
A 27-year-old man walks into the emergency
department in an agitated state. He complains
of severe abdominal pain and eventually becomes
combative, requiring five-point restraint.
His vital signs show elevated blood pressure
and tachycardia. When a straight catheter is inserted,
reddish urine enters the Foley bag. The
urine is negative for RBCs, and a toxicity
screen is negative. His doctor suspects a porphyria;
laboratory tests for urine porphobilinogen
are positive. Which of the following enzyme
defi ciencies is responsible for this
patient’s disorder?
(A) Aminolevulinate dehydratase
(B) Aminolevulinate synthase
(C) Ferrochelatase
(D) Heme oxygenase
(E) Porphobilinogen deaminase
(F) Uroporphyrinogen decarboxylase
(G) Uroporphyrinogen III cosynthase
E. (E) Porphobilinogen deaminase
aka Uroporphyrinogen-1- synthase
Sun sensitivity –> blistering
Tea colored urine
Excess hair growth
Hyperpigmentation
- associated with
- increased lab
- deficiency
Porphyria cutanea tarda
Associated with hepatitis C and alcoholism
Increase LFTs
Uroporphyrinogen decarboxylase
AD
Build up uroporphyrinogen III
Lead poisoning affects
delta-ALA dehydratase
Ferrochelatase
Increased levels of protoporphyrin
A 3-year-old boy presents to his pediatrician with irritability, an ataxic gait, and regression
of speech to single words. During the interview, the patient is constantly putting objects
in his mouth. Laboratory values are signifi cant for a hemoglobin level of 8.3 g/dL. Which of
the following etiologies should be suspected in this patient?
(A) Acetaminophen toxicity
(B) Aspirin toxicity
(C) Button battery ingestion
(D) Lead poisoning
(E) Organophosphate absorption
(F) Tricyclic antidepressant overdose
D. Lead poisoning
Abdominal pain Renal failure Mental deterioration Foot/ wrist drop Memory loss
Tx
Lead poisoning
EDTA
Succinmer
Severe poisoning in child
- Dimercaprol + succimer
Tumors that cause erythrocytosis
“Potentially Really High Hematocrit”
Pheochromocytomas
Renal cell carcinoma
Hepatocellular carcinoma
Hemangioblastoma
RL step of Heme synthesis
delta-ALA synthase
Which substance and cofactor are required for generation of GABA
Glutamate
B6
Plummer-Vinson syndrome
Iron deficiency anemia
Esophageal webs
Dysphagia
+/- atrophic glossitis
Alpha thalassemia trait/ minor
2 abnormal alpha alleles
2 normal alpha
Hemoglobin H
3 abnormal alpha alleles
Lots of beta
Hemoglobin Bart
4 abnormal alpha
Hydrops fetalis
Death
Chipmunk face
Hair on end appearance on xray of skull
Target cells
Beta thalassemia Major
Increase Hemoglobin F
2 alpha, 2 gamma
Sideroblastic anemia Labs
Treatmetn
Increased serum iron
Increased ferritin
Tx: B6
Test for beta thalassemia minor
Hemoglobin electrophoresis
What is the RL step of beta oxidation of fatty acids
Carnitine acyltransferase I
Cofactors required for function of pyruvate dehydrogenase?
These cofactors are also required for?
Tender Loving Care For Noone
TPP Lipoic acid CoA FAD NAD
Alpha-ketoglutarate dehydrogenase
Hypersegmented neutrophils
Glossitis
Increased homocysteine
Normal methylmalonic acid
Folate deficiency
Hypersegmented neutrophila Anemia Glossitis Neurologic deficits Increased homocysteine INcreased MMA
B12 deficiency
Perncious anemia
B12 deficiency
Intrinsic factor def
Anemia
Increased CMV
Hypersegmented neutrophils Orotic acid in urine
-deficiency
Orotic aciduria
Deficiency of UMP synthase
Causes of aplastic anemia
Radiation Benzene Drugs - Chloramphenicol - Cancer drugs Viral infections - ParvoB19 - EBV - HIV Fanconi anemia - inherited defect of DNA repair
Megaloblastic anemia + peripheral neuropathy
B12 deficiency
HIV positive patient with macrocytic anemia
Zidovudine
What disorder is associated with each of the following?
- HTN + hypokalemia + metabolic alkalosis
- Fever + night sweats + WL
- Adrenal hemorrhage due to meningococcemia
- Blue sclerae
- Hyperphagia + hypersexuality + hyperorality + hyperdocility
- Nystagmus + intention tremor + scanning speech
- Lower extremity purpura + arthralgias + renal disease
- hyperaldosteronism
- B symptoms of lymphoma
- Waterhouse frridrichsen syndrome
- Osteogenesis imperfecta
- Kluver-Bucy syndrome
(B/L amygdala) - Charcot triad of MS
- Henoch-Schelein purpura
Cold agglutinins
- what it is
- nearly always
- occur with
Ab against RBC that interact more strongly at low temps
IgM
Occur regularly in infections with EBV or mycoplasma
Warm agglutinins
- what is it
- nearly always
- Seen in
Ab against RBC that react at body temp
IgG
Seen in: - EBV, HIV - Lupus - Malignancies (CLL, non-hodgkin lymphoma) - Congenital immune abnormalities
Direct coombs
Using Ab to detect Ab already bound to RBCs
Indirect coombs
New blood see if Ab bind
Test prior to transfusion and screen for maternal Ab to fetus blood
MCHC
mean corpuscular hemoglobin content
Increased MCHC Increased RDW Splenomegaly Jaundice Pigmented gallstones
(+) osmotic fragility test
(+) Eosin-5- maleimide
Hereditary spheocytosis
Defect of proteins
- Ankyrin, spectrin, Band 3, Protein 4.2
Eosin-5- maleimide
- reduced binding to RBCs indicated band 3 deficiency
Associated with G6PD deficiency
“Spleen purges Nasty Inclusion From Damaged Cells”
Sulfonamides Primiquine Nitrofurantoin Isoniazid Fava Beans Dapsone Chloroquine
Paroxysmal nocturnal hemoglobinuria
RBCs missing surface markers
CD55 CD59
Complement attacks and lyses RBCs
Ham’s test
A 45-year-old woman arrives in the emergency department complaining of intense pain in her upper abdomen for the past 4 hours. She had a similar episode in the past, but it went away within an hour. Her history is significant for a recent flu-like infection and a prolonged feeling of fatigue and general exhaustion. Physical examination reveals that her sclerae are icteric, her palate is abnormally pigmented, and her skin has a yellow hue. Ultrasound shows radiopaque gallstones. A Coombs’ test is negative.
A peripheral blood smear shows small RBCs, several of which have no central pallor.
Which of the following is the most likely cause of this patient’s condition?
(A) A mutation in the gene encoding ankyrin
(B) A mutation in the glucose 6-phosphate dehydrogenase
gene
(C) Circulating antibodies targeted against
erythrocytes
(D) Iron deficiency anemia
(E) RBC hemolysis because of a mechanical
heart valve
(A) A mutation in the gene encoding ankyrin
Hereditary spheocytsosi
A 20-year-old African-American man develops
anemia after being treated for a urinary tract infection.
A peripheral blood smear shows RBC
lysis and precipitates of hemoglobin within the
RBCs. Which of the following drug classes
most likely caused his hemolytic anemia?
(A) Aminoglycosides
(B) Fluoroquinolones
(C) Macrolides
(D) Sulfonamides
(E) Tetracyclines
D. Sulfonamides
G6PD deficiency
A 30-year-old, previously healthy man from Lagos,
Nigeria, passes dark brown urine 2 days after starting the
prophylactic antimalarial drug primaquine. On physical examination,
he appears pale and is afebrile. There is no organomegaly.
Laboratory studies show that his serum haptoglobin
level is decreased. Which of the following is the most likely
explanation of these findings?
A Antibody-mediated hemolysis
B Impaired DNA synthesis
C Impaired globin chain synthesis
D Increased susceptibility to complement-induced lysis
E Mechanical fragmentation of RBCs as a result of
vascular narrowing
F Oxidative injury to hemoglobin
G Reduced deformability of RBC membrane
F Oxidative injury to hemoglobin
G6PD deficiency
A 16-year-old boy notes passage of dark urine. He has a
history of multiple bacterial infections and venous thromboses for the past 10 years, including portal vein thrombosis in the previous year. On physical examination, his right leg is swollen and tender. CBC shows hemoglobin, 9.8 g/dL; hematocrit,
29.9%; MCV, 92 μm3; platelet count, 150,000/mm3; and WBC
count, 3800/mm3 with 24% segmented neutrophils, 1% bands, 64% lymphocytes, 10% monocytes, and 1% eosinophils. He has a reticulocytosis, and his serum haptoglobin level is very
low. A mutation affecting which of the following gene products
is most likely to give rise to this clinical condition?
A β-Globin chain
B Factor V
C Glucose-6-phosphate dehydrogenase
D Phosphatidylinositol glycan A (PIGA)
E Prothrombin G20210A
F Spectrin
D Phosphatidylinositol glycan A (PIGA)
Paroxysmal nocturnal hemoglobinuria
PIGA gene mutation
Prevents expression of certain proteins that are required as glycolipid anchor
- A 32-year-old woman from Hanoi, Vietnam, gives birth
at 34 weeks’ gestation to a markedly hydropic stillborn male
infant. Autopsy findings include hepatosplenomegaly and
cardiomegaly, serous effusions in all body cavities, and generalized
hydrops. No congenital anomalies are noted. There
is marked extramedullary hematopoiesis in visceral organs.
Which of the following hemoglobins is most likely predominant
on hemoglobin electrophoresis of the fetal RBCs?
A Hemoglobin A1
B Hemoglobin A2
C Hemoglobin Bart’s
D Hemoglobin E
E Hemoglobin F
F Hemoglobin H
C Hemoglobin Bart’s
alpha-thalassemia major
chr 16
- A 3-year-old boy from Sicily has a poor appetite and
is underweight for his age and height. Physical examination shows hepatosplenomegaly. The hemoglobin concentration is 6 g/dL, and the peripheral blood smear shows severely hypochromic and microcytic RBCs. The total serum iron level is normal, and the reticulocyte count is 10%. A radiograph of the skull shows maxillofacial deformities and expanded marrow spaces. Which of the following is the most likely cause of this child’s illness?
A Imbalance in α-globin and β-globin chain
production
B Increased fragility of erythrocyte membranes
C Reduced synthesis of hemoglobin F
D Relative deficiency of vitamin B12
E Sequestration of iron in reticuloendothelial cells
A Imbalance in α-globin and β-globin chain
production
beta-thalassemia major
bronze diabetes
12 A 17-year-old girl has had a history of fatigue and weakness
for her entire life. She has not undergone puberty. On
physical examination, secondary sex characteristics are not
well developed. She has hepatosplenomegaly. CBC shows hemoglobin
of 9.1 g/dL, hematocrit of 26.7%, MCV of 66 μm3,
platelet count of 89,000/mm3, and WBC count of 3670/mm3.
The appearance of the peripheral blood smear is shown in the
figure. Additional laboratory findings include serum glucose
of 144 mg/dL, TSH of 6.2 mU/mL, and ferritin of 679 ng/mL.
A mutation in a gene encoding for which of the following is
most likely to be present in this girl?
A Ankyrin
B β-Globin
C G6PD
D HFE
E NADPH oxidase
B β-Globin
beta-thalassemia
- intermediate severity
10 A 10-year-old child has experienced multiple episodes
of pneumonia and meningitis with septicemia since infancy.
Causative organisms include Streptococcus pneumoniae and
Haemophilus influenzae. On physical examination, the child
has no organomegaly and no deformities. Laboratory studies
show hemoglobin of 9.2 g/dL, hematocrit of 27.8%, platelet
count of 372,000/mm3, and WBC count of 10,300/mm3. A hemoglobin
electrophoresis shows 1% hemoglobin A2, 7% hemoglobin
F, and 92% hemoglobin S. Which of the following is
the most likely cause of the repeated infections in this child?
(RBC white white center) A Absent endothelial cell expression of adhesion molecules B Diminished hepatic synthesis of complement proteins C Impaired neutrophil production D Loss of normal splenic function E Reduced synthesis of immunoglobulins
D Loss of normal splenic function
Sickle cell anemia
13 A 12-year-old boy has a history of episodes of severe abdominal,
chest, and back pain since early childhood. On physical
examination, he is afebrile, and there is no organomegaly.
Laboratory studies show hemoglobin of 11.2 g/dL, platelet
count of 194,000/mm3, and WBC count of 9020/mm3. The peripheral
blood smear shows occasional sickled cells, nucleated
RBCs, and Howell-Jolly bodies. Hemoglobin electrophoresis
shows 1% hemoglobin A2, 6% hemoglobin F, and 93% hemoglobin
S. Hydroxyurea therapy is found to be beneficial in
this patient. An increase in which of the following is the most
likely basis for its therapeutic efficacy?
A Erythrocyte production B Overall globin chain synthesis C Oxygen affinity of hemoglobin D Production of hemoglobin A E Production of hemoglobin F
E Production of hemoglobin F
Sickle cell anemia
19 34-year-old woman reports becoming increasingly tired
for the past 5 months. On physical examination, she is afebrile
and has mild splenomegaly. Laboratory studies show a hemoglobin
concentration of 10.7 g/dL and hematocrit of 32.3%. The
peripheral blood smear shows spherocytes and rare nucleated
RBCs. Direct and indirect Coombs test results are positive at
37° C, although not at 4° C. Which of the following underlying
diseases is most likely to be diagnosed in this patient?
A Escherichia coli septicemia
B Hereditary spherocytosis
C Infectious mononucleosis
D Mycoplasma pneumoniae infection
E Systemic lupus erythematosus
E Systemic lupus erythematosus
Warm autoimmune hemolytic anemia secondary to SLE
20 A 22-year-old woman has experienced malaise and a
sore throat for 2 weeks. Her fingers turn white on exposure
to cold. On physical examination, she has a temperature of
37.8° C, and the pharynx is erythematous. Laboratory findings
include a positive monospot (heterophile antibody) test
result. Direct and indirect Coombs test results are positive at
4° C, although not at 37° C. Which of the following molecules
bound on the surfaces of the RBCs most likely accounts for
these findings?
A α2-Macroglobulin
B Complement C3b
C Fibronectin
D Histamine
E IgE
B Complement C3b
Cold agglutinin disease
38 A 28-year-old, previously healthy man has noted
increasing fatigue for the past 6 months and formation of bruises
after minimal trauma. Over the past 2 days, he has developed
a cough. On physical examination, his temperature is 38.9° C,
and he has diffuse rales in both lungs. He has no hepatosplenomegaly
and no lymphadenopathy. Laboratory findings include
a sputum culture positive for Streptococcus pneumoniae,
hemoglobin of 7.2 g/dL, hematocrit of 21.7%, platelet count of 23,400/mm3, WBC count of 1310/mm3, prothrombin time of 13 seconds, partial thromboplastin time of 28 seconds, and total bilirubin of 1 mg/dL. The ANA test result is negative. What is the most likely explanation of these findings?
A Hematopoietic stem cell defect
B Hemolysis of antibody-coated cells
C Increased susceptibility to lysis by complement
D Metastatic adenocarcinoma to bone marrow
E Secondary hypersplenism
A Hematopoietic stem cell defect
Aplastic anemia
47 A 37-year-old woman has noted an excessively heavy
menstrual flow each of the past 6 months. She also has noticed
increasing numbers of pinpoint hemorrhages on her lower extremities
in the past month. Physical examination shows no organomegaly
or lymphadenopathy. CBC shows hemoglobin of
14.2 g/dL, hematocrit of 42.5%, MCV of 91 μm3, platelet count
of 15,000/mm3, and WBC count of 6950/mm3. On admission
to the hospital, she has melena and after a transfusion of platelets,
her platelet count does not increase. Which of the following
describes the most likely basis for her bleeding tendency?
A Abnormal production of platelets by
megakaryocytes
B Defective platelet-endothelial interactions
C Destruction of antibody-coated platelets by the spleen
D Excessive loss of platelets in menstrual blood
E Suppression of pluripotent stem cell division
C Destruction of antibody-coated platelets by the spleen
Bleeding due to low platelet count
Idiopathic chronic immune thrombocytopenia purpura (ITP)
48 A 9-year-old boy has developed prominent bruises on
his extremities over the past week. On physical examination,
he has ecchymoses and petechiae on his arms and legs.
Laboratory studies show hemoglobin, 13.8 g/dL; hematocrit,
41.9%; MCV, 93 μm3; platelet count, 11,300/mm3; and WBC
count, 7720/mm3. He had respiratory syncytial virus pneumonia
3 weeks ago. His condition improves with corticosteroid
therapy. Which of the following abnormalities is most likely to
cause his hemorrhagic diathesis?
A Antiplatelet antibodies
B Bone marrow aplasia
C Glycoprotein IIb/IIIa dysfunction
D Vitamin C deficiency
E Von Willebrand factor metalloproteinase deficiency
A Antiplatelet antibodies
Acute immune thrombocytopenic purpura (ITP) and chronic ITP
49 A 21-year-old woman known to have a protein C deficiency
develops recurrent pulmonary thromboembolism and
is placed on anticoagulant therapy. Two weeks after initiation
of this therapy, she has a sudden change in mental status and
experiences difficulty speaking and swallowing. A cerebral
angiogram shows a left middle cerebral artery occlusion. Laboratory
studies show hemoglobin of 13 g/dL, platelet count of
65,400/mm3, WBC count of 5924/mm3, prothrombin time of
12 seconds, and partial thromboplastin time of 51 seconds. The
anticoagulant therapy is discontinued. Which of the following
pharmacologic agents used as an anticoagulant in this patient
is most likely to have caused these findings?
A Acetylsalicylic acid (aspirin)
B Heparin
C Tissue plasminogen activator
D Urokinase
E Warfarin
B Heparin
Heparin-induced thrombocytopenia
45 A 23-year-old woman in her 25th week of pregnancy has
felt no fetal movement for the past 3 days. Three weeks later,
she still has not given birth and suddenly develops dyspnea
with cyanosis. On physical examination, her temperature is 37°
C, pulse is 106/min, respirations are 23/min, and blood pressure
is 80/40 mm Hg. She has large ecchymoses over the skin
of her entire body. A stool sample is positive for occult blood.
Laboratory studies show an elevated prothrombin time and
partial thromboplastin time. The platelet count is decreased,
plasma fibrinogen is markedly decreased, and fibrin split products
are detected. A blood culture is negative. Which of the following
is the most likely cause of her bleeding diathesis?
A Consumption of coagulation factors
B Defects in platelet aggregation
C Increased vascular fragility
D Reduced production of platelets
E Toxic injury to the endothelium
A Consumption of coagulation factors
Thrombocytopenia
Increased PT and PTT
Fibrin split products
Low fibrinogen
Disseminated intravascular coagulation (DIC)
50 A 56-year-old woman suffers the sudden onset of headache
and photophobia, and her condition worsens for the next 2
days. On physical examination, she has a temperature of 38° C
and is disoriented. CBC shows hemoglobin of 11.2 g/dL, hematocrit
of 33.7%, MCV of 94 μm3, platelet count of 32,000/
mm3, and WBC count of 9900/mm3. The peripheral blood
smear shows schistocytes. The serum urea nitrogen level is 38
mg/dL, and the creatinine level is 3.9 mg/dL. Which of the
following is the most likely diagnosis?
A Autoimmune hemolytic anemia
B β-Thalassemia major
C Disseminated intravascular coagulation
D Idiopathic thrombocytopenic purpura
E Paroxysmal nocturnal hemoglobinuria
F Thrombotic thrombocytopenic purpura
F Thrombotic thrombocytopenic purpura
TTP
54 A clinical study is performed involving adult patients
diagnosed with microangiopathic hemolytic anemia. A subgroup
of patients who had fever or diarrhea preceding the
initial diagnosis of anemia were excluded. The patients had
schistocytes present on peripheral blood smears. Some of these
patients were found to have a deficiency of a metalloproteinase
known as ADAMTS13. Which of the following conditions
were the patients with this deficiency most likely to have?
A Disseminated intravascular coagulation (DIC)
B Hemolytic-uremic syndrome (HUS)
C Heparin-induced thrombocytopenia (HIT)
D Idiopathic thrombocytopenic purpura (ITP)
E Thrombotic thrombocytopenic purpura (TTP)
E Thrombotic thrombocytopenic purpura (TTP)
55 A 45-year-old woman has had episodes of blurred vision
and headaches for the past 6 months. She has had worsening
confusion with paresthesias over the past 3 days. On
physical examination, she has a temperature of 39.6° C, pulse
of 100/min, respiratory rate of 20/min, and blood pressure
of 80/50 mm Hg. Petechial hemorrhages are noted over her
trunk and extremities. Laboratory findings include hemoglobin,
10.9 g/dL; hematocrit, 34%; MCV, 96 μm3; platelet count,
28,000/mm3; and WBC count, 8500/mm3. Fragmented RBCs
are noted on her peripheral blood smear. Blood urea nitrogen
is 40 mg/dL, and serum creatinine is 3.1 mg/dL. Which of the
following is the most likely underlying cause for her findings?
A Circulating toxin that injures capillary endothelium
B Decreased factor VIII activity
C Defective ADP-induced platelet aggregation
D Formation of autoantibodies to platelet glycoproteins
IIb/IIIa and Ib-IX
E Inappropriate release of thromboplastic substances
into blood
F Presence of antibodies against ADAMTS13
metalloproteinase
F Presence of antibodies against ADAMTS13
Neurlogic abnromalities Fever Thrombocytopenia microangiopathic hemolytic anemia Renal failure
Thrombotic thrombocytopenic purpura (TTP)
deficiency of von Willebrand factor (vWF) metalloproteinase (ADMTS13)
52A 23-year-old woman has a history of easy bruising.
Physical examination shows multiple bruises ranging in color
from red to blue to purple on her arms and legs. There is no organomegaly,
and no deformities are noted. Laboratory studies
show hemoglobin, 9.5 g/dL; hematocrit, 28.2%; platelet count,
229,300/mm3; WBC count, 7185/mm3; prothrombin time, 12
seconds; and partial thromboplastin time, 38 seconds. A 1:1
dilution of the patient’s plasma with normal pooled plasma
corrects the partial thromboplastin time. Ristocetin-dependent
platelet aggregation in patient plasma is markedly reduced.
Factor VIII activity is 30% (reference range 50% to 150%).
Which of the following is the most likely potential consequence
of this disease?
A Bone marrow failure from aplasia
B Excessive bleeding after oral surgery
C Increasing difficulty with joint mobility
D Myeloproliferative disorder
E Recurrent deep venous thrombosis
B Excessive bleeding after oral surgery
Normal platelet count
Prolonged bleeding time
Von Willebrand disease
58 A 15-year-old girl has a history of easy bruising and
hemorrhages. Since menarche at the age of 13 years, she has had menometrorrhagia. On physical examination, she displays joint deformity and has decreased mobility of the ankles, knees, and wrists. Laboratory studies show hemoglobin, 11.8 g/dL; hematocrit, 35.1%; platelet count, 267,000/mm3;
WBC count, 5960/mm3; prothrombin time, 13 seconds; and
partial thromboplastin time, 60 seconds. A 1:1 dilution of the patient’s plasma with normal pooled plasma corrects the partial thromboplastin time. Which of the following is the most
likely diagnosis?
A Antiphospholipid syndrome
B Hemophilia B
C Idiopathic thrombocytopenic purpura
D Thrombotic thrombocytopenic purpura
E Von Willebrand disease
B Hemophilia B
PTT corrected by nromal pooled plasma
Factor IX deficiency
56 A 12-year-old boy has had worsening problems with joint
mobility involving his arms and legs, particularly his knees and
ankles, for the past 6 years. He has been receiving therapy for
this condition. His grandfather had a similar condition and died
at age 25 years. On physical examination, he has no visible petechiae
or areas of purpura. Laboratory studies show that prothrombin
time is 12 seconds, and partial thromboplastin time
is 52 seconds. After addition of an equivalent aliquot of normal
plasma, the partial thromboplastin time is 30 seconds. Hemoglobin
is 12.9 g/dL, platelet count is 238,500/mm3, and WBC
count is 6620/mm3. His platelet function studies are normal.
What is the most likely inheritance pattern for his condition?
A Autosomal dominant
B Autosomal recessive
C Confined placental mosaicism
D Germline mutation
E X-linked recessive
E X-linked recessive
Hemophilia A
monitored with Factor VIII
59 A 16-year-old girl has had frequent nosebleeds since
childhood. Her gums bleed easily, even with routine tooth
brushing. She has experienced menorrhagia since menarche
at age 13 years. On physical examination, there are no abnormal
findings. Laboratory studies show hemoglobin,
14.1 g/dL; hematocrit, 42.5%; MCV, 90 μm3; platelet count,
277,400/mm3; and WBC count, 5920/mm3. Her platelets fail
to aggregate in response to ADP, collagen, epinephrine, and
thrombin. The ristocetin agglutination test result is normal.
There is a deficiency of glycoprotein IIb/IIIa. Prothrombin time is 12 seconds, and partial thromboplastin time is 28 seconds.
What is the most likely diagnosis?
A Disseminated intravascular coagulation
B Glanzmann thrombasthenia
C Immune thrombocytopenic purpura
D Vitamin C deficiency
E Von Willebrand disease
B Glanzmann thrombasthenia
AR
An 8-year-old boy is brought to the pediatrician
after his parents noticed very dark urine in the
toilet earlier that morning. Initial laboratory
studies show intravascular hemolysis; further
testing shows that his RBCs are susceptible to
complement-mediated lysis. This patient most
likely has which of the following conditions?
(A) Autoimmune hemolytic anemia
(B) Common bile duct stricture
(C) Hereditary spherocytosis
(D) Paroxysmal nocturnal hemoglobinuria
(E) Thrombotic thrombocytopenic purpura
(D) Paroxysmal nocturnal hemoglobinuria
- Low-molecular-weight heparins (LMWH) are
distinct from unfractionated heparin in several
ways. Which of the following is the primary
target of LMWH?
(A) Antithrombin III
(B) Factor IIa
(C) Factor VII
(D) Factor Xa
(E) Factors II, IX, and X
(D) Factor Xa
LMWH act on Xa
- A 7-year-old African-American boy is brought
to see his pediatrician. His father says he has
noticed that the boy has been complaining of
right knee pain for the past week. On physical
exam, multiple ecchymoses are noted on both
upper and lower extremities. His father claims
that the boy has always bruised easily, and he
has recently learned how to ride a bicycle.
Which of the following elements of the coagulation
cascade is most likely to be missing in
this child?
(A) Antithrombin III
(B) Factor VII
(C) Factor VIII
(D) Factor IX
(E) Protein C
(C) Factor VIII
Hemophilia A
X linked
- A 16-year-old boy is brought to the emergency
department because of the acute onset of fever,
chills, and a productive cough. X-ray of the
chest shows an infi ltrate restricted to the left
lower lobe. Samples taken of the sputum show
α-hemolytic gram-positive cocci in pairs. The
patient says that he has had similar infections
over the past year. A peripheral blood smear is
done, and results show several sickle-shaped
RBCs. Which of the following explains why
this patient is susceptible to this particular type
of infection?
(A) Bone marrow infi ltration resulting in neutropenia
and compromised immune function
(B) Large vessel occlusions in the cerebral vasculature
resulting in neurologic events and
aspiration pneumonia
(C) Microvascular infarcts resulting in pulmonary
failure
(D) Microvascular infarcts resulting in splenic
dysfunction
(E) Vaso-occlusion in the renal medulla
(D) Microvascular infarcts resulting in splenic
dysfunction
Sickle cell disease
14.A child is brought to the pediatrician because
her parents are concerned about lead poisoning
since their house is known to contain leadbased
paint. A complete blood cell count reveals
anemia. Lead poisoning causes anemia
because it does which of the following?
(A) Disrupts heme synthesis by causing decreased
iron absorption from the gut
(B) Disrupts heme synthesis by increasing the
activity of aminolevulinate dehydratase
(C) Disrupts heme synthesis by inhibiting ferrochelatase
(D) Disrupts hemoglobin function by binding
to hemoglobin with high affi nity, preventing
oxygen binding
(E) Disrupts RBC DNA synthesis, causing
megaloblastic changes in RBCs
(C) Disrupts heme synthesis by inhibiting ferrochelatase
Lead inhibits (ALA) dehydratase Ferrochelatase
27 A 3-year-old girl was in her usual state of good
health 1 month ago when she developed an
acute viral upper respiratory infection. She
now presents to the emergency department
with nonblanching purple skin lesions. The
rest of her physical examination is unremarkable.
The complete blood count demonstrates
a low platelet count, while the peripheral
blood smear is notable only for large platelets.
Which of the following laboratory fi ndings
would most likely be present in this patient?
(A) Antiplatelet antibodies
(B) Decreased megakaryocytes on bone marrow
biopsy
(C) IgA defi ciency
(D) Increased fi brin split products
(E) Vitamin K defi ciency
(A) Antiplatelet antibodies
Idiopathic thrombocytopenic purpura (ITP)
36 Hydrops fetalis occurs in the setting of a certain
type of thalassemia. What is the underlying
mechanism leading to this event?
(A) Excess α-globin chains binding tighter to
oxygen
(B) Excess α-globin chains binding weaker to
oxygen
(C) Excess β-globin chains binding tighter to
oxygen
(D) Excess β-globin chains binding weaker to
oxygen
(E) Excess gamma-globin chains binding
tighter to oxygen
(F) Excess gamma-globin chains binding
weaker to oxygen
(E) Excess gamma-globin chains binding
tighter to oxygen
alpha thalassemia
40 A 28-year-old woman comes to the physician
concerned about an excessive amount of bleeding
from her gums when she brushes her teeth.
Her laboratory results show an increased partial
thromboplastin time and an increased bleeding
time, but are otherwise unremarkable.
Which of the following treatments will most
likely alleviate this patient’s symptoms?
(A) Cryoprecipitate
(B) Factor VIII concentrate
(C) Fresh frozen plasma
(D) Low-molecular-weight heparin
(E) Protamine sulfate
(A) Cryoprecipitate
Von Willebrand disease
42 A 62-year-old woman presents to the clinic
complaining of frequent bleeding while brushing
her teeth and easy bruising. She reports
she recently had pneumonia and was treated
with a broad-spectrum antibiotic. Laboratory
tests show:
Prothrombin time: 18 seconds
Partial thromboplastin time: 37 seconds
Platelet count: 231,000/mm³
Hematocrit: 37%
WBC count: 4800/mm³
The cofactor that is defi cient in this patient is
needed for the carboxylation of glutamate residues
of which of the following?
(A) Factors II, VII, VIII, and X
(B) Factors VII, VIII, IX, and XII
(C) Proteins C and S and factors IX, X, XI, and
XII
(D) Proteins C and S and factors XII, IX, and X
(E) Proteins C and S, prothrombin, and factors
VII, IX, and X
(E) Proteins C and S, prothrombin, and factors
VII, IX, and X
Prolong pT
Deficiency of factor in extrinsic pathways
- A 20-year-old African-American man develops
anemia after being treated for a urinary tract infection.
A peripheral blood smear shows RBC
lysis and precipitates of hemoglobin within the
RBCs. Which of the following drug classes
most likely caused his hemolytic anemia?
(A) Aminoglycosides
(B) Fluoroquinolones
(C) Macrolides
(D) Sulfonamides
(E) Tetracyclines
(D) Sulfonamides
G6PD deficiency
44 Several drugs are used to prevent myocardial
infarction in patients with acute coronary syndrome.
One class of drugs binds to the glycoprotein
receptor IIb/IIIa on activated platelets,
thereby interfering with platelet aggregation.
This prevents renewed formation of clots that
could block the lumen of the cardiac vessels.
Which of the following is an example of this
class of drug?
(A) Abciximab
(B) Clopidogrel
(C) Leuprolide
(D) Selegiline
(E) Ticlopidine
(A) Abciximab
47 A 70-year-old man comes to his physician for a
routine physical examination. Although he is
asymptomatic, a blood test shows an abnormal
level of immunoglobulin. After further testing,
he is diagnosed with monoclonal gammopathy
of undetermined signifi cance. Which of the following is the current treatment for monoclonal
gammopathy of undetermined signifi -
cance?
(A) Alendronate
(B) Anticoagulation
(C) High-dose steroids
(D) No treatment
(E) Vinca alkaloids
(D) No treatment
Monoclonal gammopathy of undetermined significant (MGUS)
48 An 8-year-old boy has a chronic history of severe
hemolytic anemia, hepatosplenomegaly,
and maxillary overgrowth. He has received
blood transfusions since early infancy but has
not received a transfusion in over 4 months. A
hemoglobin electrophoresis shows marked elevation
of HbF, increased HbA2, and absence of
HbA1. Which of the following diagnoses is
most consistent with this patient’s electrophoresis?
(A) α-Thalassemia minor
(B) β-Thalassemia major
(C) β-Thalassemia minor
(D) Glucose 6-phosphate dehydrogenase defi -
ciency
(E) HbH disease
(F) RBCs containing hemoglobin Barts
(B) β-Thalassemia major
Thalassemias
Sickle cell disease
- mutation
- xray
- tx
HbS mutation
Point mutation on beta globulin
Glu –> Val
Hair on end appearance on Xray skull
– bone marrow hyperplasia
Hydroxyurea
-increases production of HbF
Order of bands on electrophoresis
Left to right C S F A
Ham’s test
Osmotic fragility test
Paroxysmal nocturnla hemoglobinuria
Hereditary spherocytosis
Women develops muscle cramps and darkening of urine after exercising. Diagnosis?
McArdle disease
Von Willebrand factor (vWF)
- fxn
- works with
- defieicny
Complexes with and stabilizes factor VIII
Platelet adhesion to vessel wall and other platelets
Deficiency increase PTT
Increase bleeding time
Life span platelets
8-10 days
Platelet Adhesion steps
Endothelial damage
Exposure underlying collagen
Damaged cells release contents
vWF binds exposed collagen and bind glycoprotein receptor GpIb on surface of platelet
Platelet Activation
Platelet Aggregation
Activation
- platelets grow pseudopods help bind in injury site
- secrete substances
Aggregation
- Activated platelet secretes ADP (adenosine diphosphate)
- ADP binds to receptor on surface of platelet
- Triggers expression of glycoprotein IIB/IIIA to come to surface of platelet
- binds fibrinogen, forms series of crosslinks between platelets
Branching rods on oral infection
Actinomyces israelii
Eczema
Recurrent infections
Thrombocytopenia
Wiskott-aldrich syndrome
Hemosiderinuria
Thrombosis
Paroxysmal nocturnal hemoglobinuria
Deficiency of metalloprotease ADAMTS13
Thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP)
Deficiency of metalloprotease ADAMTS13
ADAMTS13 cleaves vWF into active units
Unregulated platelet aggregation –> thrombosis
Consumption of paltelets –> thrombocytopenia
Microangiopathic hemolytic anemia
Platelet disorder presentation
Bleeding from mucous membranes
Epistaxis (nose bleeds)
Petechiae
Purpura
Increased bleeding time
Normal PT and PTT
Immune thrombocytopenia (ITP)
- labs
- tx
Autoantibodies bind glycoprotein IIb/IIIa on surface platelets
Decreased platelets
Increased megakaryocytes
(trying to make more platelets)
Steroids
IVIG
Splenectomy
Thrombotic thromocytopenic purpura symptoms
"HUNT For The TPP" Hemolysis Uremia Neurological symptoms Thrombocytopenia Fever TTP
Hemolytic uremic syndrome associated with
features
E.coli 0157:H7
Children
Hemolysis
Renal insufficiency
Thromobytopenia
Bernard-Soulier syndrome
Defect of glycoprotein Ib
Platelet unable to bind collagen
Moderate thrombocytopenia
Platelet number only slightly low
Increased bleeding time
Glanzmann thrombasthenia
Defect in glycoprotein IIb/IIIa
Abnormal platelet aggregation
Normal platelet count
Increased bleeding time
Increased PTT
Increased bleeding time
Von Willebrand disease
Ristocetin cofactor assay
Causes platelets to agglutinate if vWF is present
Von Willebrand disease
tx
DDAVP
- desmopressin (ADH analog)
ADH increase release of vWF from storage sites in endothelial cells
Decreased platelets Increased bleeding time Increased PT and PTT Decreased fibrinogen Increase fibrin split products (d-dimer)
Disseminated intravascular coagulation (DIC)
Which matches?
- Anti-gp IIb/IIIa antibodies
- ADAMTS-13 deficiency
- gp Ib defect
- gp IIb/ IIIa defect
- Von Willebrand factor defect
- Widespread activation of platelets and coagulation cascade
- ITP
- TTP-HUS
- Bernard-Soulier syndrome
- Glanzmann thromasthenia
- von Willebrand disease
- DIC
Antiplatelet antibodies
Immune thrombocytopenia
Large cells with bi-lobed nucleus
Prominent nucleoli with clearing around nucleoi
Clearing around cell
Reed Sternberg cells
Hodgkin lymphoma
48 A 35-year-old woman presents to her primary care physician with a fever of 38.3º C (101º F), night sweats, and fatigue. The patient says that she has lost about 6.7 kg (15 lb) over the past year. A CT scan demonstrates mediastinal lymphadenopathy. Biopsy of the nodes shows a small number of large cells with “owl-eye” nucleoli, multiple nuclei, and an abundance of pale cytoplasm on a background of many reactive lymphocytes, macrophages, and granulocytes. Which of the following drugs could be used to treat this condition? (A) Azathioprine (B) Cisplatin (C) Doxorubicin (D) Paclitaxel (E) β-Interferon
C. Doxorubicin
Hodgkin lymphoma
- A 34-year-old man presents to his primary care physician with night sweats, a fever of 38º C (100.2º F), and weight loss of 5 kg (12 lb) over the last 3 months. A CT scan demonstrates mediastinal
lymphadenopathy, and results of a biopsy
of the node are shown in the image.
Which of the following drugs is part of the
multidrug regimen that would be used to manage this patient’s disease?
(A) Cyclosporine (B) Hydroxyurea (C) Imatinib (D) Isoniazid (E) Vinblastine
E.(E) Vinblastine
ABVD Adriamycin Bleomycin Vinblastine Decarbazine
Hodgkin lymphoma in younger male
Lymphocyte-prdominant type
Few reed sterberg to lymphocytes
Bands of collagen, sclerosis and fibrosis
Women
Nodular sclerosing
Hodgkin lymphoma
t(14;18)
Diffuse large B cell lymphoma
-Elderly
Follicular lymphoma
t (8;14)
Burkitt lymphoma
c-MYC
Starry sky appearance
Type of burkitt lymphoma
Endemic
- Africa
- involves mandible
Sporadic
- pelvis or abdomen
Immunodeficiency assoc
- HIV
t(11;14)
Mantle cell lymphoma
Disruption of regulation of cyclin D
Non-hodgkin lymphoma associated with sjogren, hashimoto and h. pylori
Marginal cell MALToma
Most common lymphoma in U.S
Diffuse large B cell lymphoma
Owl eye nuclei
Reed-sternberg cels
Hodgkin lymphoma
Lymphoma associated with EBV
Burkitt lymphoma
Hodgkin lymphoma
Over 20% blasts in bone marrow
AML or ALL
Child Bone pain terminal deoxynucleotidy transferase (TdT) 20% blasts t(9;22)
ALL
Auer rods
20% blasts
Adult
AML
Elderly adult
CD19 CD 20
Smudge cells
CLL
t(9;22) Fatigue Abdominal pain Splenomegaly Middle aged
CML
t(9;22)
- is what
- creates
- associated with
- tx
Philadelpha chromosome
Mutation bcr-abl
Oncogene
Activated tyrosine kinase always on
CML: always present
ALL: Sometimes present
AML: rarely present
Tx: imatinib
- inhibits bcr-abl tyrosine kinase
t(15;17)
tx
M3 AML
Treat w/ all-trans retinoic acid
Acute luekemia positive for peroxidase
AML
Bence Jones proteins
Multiple myeloma
Rouleaux formation
RBC stacked like coins
MM
33 32-year-old woman presents to the emergency
department with a temperature of 38.7º
C (101.7º F), petechiae covering her abdomen,
and mental status changes. On questioning,
her husband states that “she had been fi ne
3 weeks ago but got sick real fast.” Physical examination
shows severe weakness, petechiae
and ecchymoses on the abdomen and back,
and pale conjunctiva. A laboratory study shows
severe anemia and thrombocytopenia with leukocytosis.
The peripheral blood smear demonstrates
the presence of abundant myeloblasts.
Which of the following chromosomal translocations
is most likely involved in this disorder?
(A) t(8:14) c-myc activation
(B) t(9:22), bcr-abl
(C) t(11:14), BCL1/PRAD1
(D) t(11:22), EWS gene
(E) t(15:17), PML-RAR-α
(E) t(15:17), PML-RAR-α
AML
15 A 70-year-old man has experienced increasing fatigue
for the past 6 months. On physical examination, he has nontender
axillary and cervical lymphadenopathy, but there is no
hepatosplenomegaly. The CBC shows hemoglobin, 9.5 g/dL;
hematocrit, 28%; MCV, 90 μm3; platelet count, 120,000/mm3;
and WBC count, 42,000/mm3. His peripheral blood smear
shows a monotonous population of small, round, maturelooking
lymphocytes. Flow cytometry shows these cells to
be CD19+, CD5+, and deoxynucleoti dyl transferase negative
(TdT−). Cytogenetic and molecular analysis of the abnormal
cells in his blood are most likely to reveal which of the following
alterations?
A Clonal rearrangement of immunoglobulin genes
B Clonal rearrangement of T-cell receptor genes
C t(8;14) leading to c-MYC overexpression
D t(9;22) leading to BCR-ABL rearrangement
E t(14;18) leading to BCL2 overexpression
A Clonal rearrangement of immunoglobulin genes
CLL
17 A 4-year-old boy has appeared listless during the
past week. He exhibits irritability when his arms or legs are
touched. In the past 2 days, large ecchymoses have appeared
on the right thigh and left shoulder. CBC shows hemoglobin,
9.3 g/dL; hematocrit, 28.7%; MCV, 96 μm3; platelet count,
45,000/mm3; and WBC count, 13,990/mm3. Examination of
the peripheral blood smear shows blasts that lack peroxidasepositive
granules, but contain PAS-positive aggregates and
stain positively for deoxynucleoti dyl transferase negative
(TdT−). Flow cytometry shows the phenotype of blasts to be
CD19+, CD3−, and sIg−. Which of the following is the most
likely diagnosis?
A Acute lymphoblastic leukemia
B Acute myelogenous leukemia
C Chronic lymphocytic leukemia
D Chronic myelogenous leukemia
E Idiopathic thrombocytopenic purpura
A Acute lymphoblastic leukemia
ALL
8 A 36-year-old woman has a cough and fever for 1 week.
On physical examination, her temperature is 38.3° C. She has
diffuse crackles in all lung fields. A chest radiograph shows
bilateral extensive infiltrates. CBC shows hemoglobin, 13.9 g/
dL; hematocrit, 42%; MCV, 89 μm3; platelet count, 210,000/
mm3; and WBC count, 56,000/mm3 with 63% segmented neutrophils,
16% bands, 7% metamyelocytes, 3% myelocytes, 1%
blasts, 8% lymphocytes, and 2% monocytes. A bone marrow
biopsy is obtained and shows normal maturation of myeloid
cells. Which of the following is the most likely diagnosis?
A Chronic myelogenous leukemia
B Hairy cell leukemia
C Hodgkin lymphoma, lymphocyte depletion type
D Leukemoid reaction
E Myelodysplastic syndrome
D Leukemoid reaction
CML
14 A 14-year-old boy complains of discomfort in his chest
that has worsened over the past 5 days. On physical examination,
he has generalized lymphadenopathy. A chest radiograph
shows clear lung fields, but there is widening of the mediastinum.
A chest CT scan shows a 10-cm mass in the anterior
mediastinum. A biopsy specimen of the mass is obtained and
microscopically shows effacement by lymphoid cells with
lobulated nuclei having delicate, finely stippled, nuclear chromatin.
There is scant cytoplasm, and many mitotic figures are
seen. The cells express deoxynucleoti dyl transferase negative
(TdT−), CD2, and CD7 antigens. Molecular analysis reveals a
point mutation in the NOTCH1 gene. The oncologist tells the
parents that chemotherapy can be curative in vast majority of
such cases. What is the most likely diagnosis?
A Burkitt lymphoma
B Follicular lymphoma C Hodgkin lymphoma, nodular sclerosing type
D Lymphoblastic lymphoma
E Mantle cell lymphoma
F Small lymphocytic lymphoma
D Lymphoblastic lymphoma
ALL
18 A 7-year-old boy has complained of a severe headache
for the past week. On physical examination, there is tenderness
on palpation of long bones, hepatosplenomegaly, and
generalized lymphadenopathy. Petechial hemorrhages are
present on the skin. Laboratory studies show hemoglobin,
8.8 g/dL; hematocrit, 26.5%; platelet count, 34,700/mm3; and
WBC count, 14,800/mm3. A bone marrow biopsy specimen
shows 100% cellularity, with almost complete replacement
by a population of large cells with scant cytoplasm lacking
granules, delicate nuclear chromatin, and rare nucleoli. His
oncologist is confident that chemotherapy will induce a complete
remission. Which of the following combinations of phenotypic
and karyotypic markers is most likely to be present in
marrow cells from this boy?
A Early pre-B CD19+ hyperdiploidy
B Early pre-B CD20+ t(9;22)
C Pre-B CD5+ normal karyotype
D Pre-B CD23+ 11q deletion
E T cell CD2+ numerous blasts
F T cell CD3+ MLL gene translocation
A Early pre-B CD19+ hyperdiploidy
ALL
20 The figure skater Sonja Henie, who won gold medals
at the 1928, 1932, and 1936 Winter Olympic Games, became
progressively fatigued in her late 50s. On physical examination,
she had palpable nontender axillary and inguinal lymph
nodes, and the spleen tip was palpable. Laboratory studies
showed hemoglobin, 10.1 g/dL; hematocrit, 30.5%; MCV, 90
μm3; platelet count, 89,000/mm3; and WBC count, 31,300/
mm3. From the peripheral blood smear shown in the figure,
which of the following is the most likely diagnosis?
A Acute lymphoblastic leukemia
B Chronic lymphocytic leukemia
C Infectious mononucleosis
D Iron deficiency anemia
E Leukemoid reaction
B Chronic lymphocytic leukemia
CLL
24 A 62-year-old man has experienced vague abdominal
discomfort accompanied by bloating and diarrhea for the past
6 months. On physical examination, there is a midabdominal
firm mass. The stool is positive for occult blood. An abdominal
CT scan shows an 11 × 4 cm mass involving the wall of the
distal ileum and adjacent mesentery. A laparotomy is performed,
and the mass is removed. Microscopically, the mass is
composed of sheets of large lymphoid cells with large nuclei,
prominent nucleoli, and frequent mitotic figures. The neoplastic
cells mark with CD19+ and CD20+ and have the BCL6 gene
rearrangement. Which of the following prognostic features is
most applicable to this case?
A Aggressive, can be cured by chemotherapy
B Aggressive, often spreads to liver, spleen, and marrow
C Aggressive, often transforms to acute leukemia
D Indolent, can be cured by chemotherapy
E Indolent, often undergoes spontaneous remission
F Indolent, survival of 7 to 9 years without treatment
A Aggressive, can be cured by chemotherapy
Diffuse large cell lymphoma of B cells
22 A 12-year-old boy has had increasing abdominal distention
and pain for the past 3 days. Physical examination of his
abdomen shows lower abdominal tenderness with tympany
and reduced bowel sounds. An abdominal CT scan shows a
7-cm mass involving the region of the ileocecal valve. Surgery
is performed and the resected mass microscopically shows
sheets of intermediate-sized lymphoid cells, with nuclei having
coarse chromatin, several nucleoli, and many mitotic figures.
A bone marrow biopsy sample is negative for this cell population.
Cytogenetic analysis of the cells from the mass shows
a t(8;14) karyotype. Flow cytometric analysis reveals 40% of
the cells are in S phase. The tumor shrinks dramatically after
a course of chemotherapy. Which of the following is the most
likely diagnosis?
A Acute lymphoblastic leukemia/lymphoma
B Burkitt lymphoma
C Diffuse large B-cell lymphoma
D Follicular lymphoma
E Plasmacytoma
B Burkitt lymphoma
Burkitt lymphoma
Sporadic
25 A 9-year-old boy living in Uganda has had increasing
pain and swelling on the right side of his face over the past 8
months. On physical examination, there is a large, nontender
mass involving the mandible, which deforms the right side of his face. There is no lymphadenopathy or splenomegaly, and
he is afebrile. A biopsy of the mass is performed and microscopic
examination shows intermediate-sized lymphocytes
with a high mitotic rate. A chromosome analysis shows a
46,XY,t(8;14) karyotype in these cells. The hemoglobin concentration
is 13.2 g/dL, platelet count is 272,000/mm3, and WBC
count is 5820/mm3. Infection with which of the following viruses
is most likely to be causally related to the development
of these findings?
A Cytomegalovirus
B Epstein-Barr virus
C Hepatitis B virus
D HIV
E Human papillomavirus
F Respiratory syncytial virus
B Epstein-Barr virus
Endemic african variety of burkitt lymphoma
23 A 55-year-old man felt a lump near his shoulder 1 week
ago. On physical examination, there is an enlarged, nontender,
supraclavicular lymph node and enlargement of the Waldeyer
ring of oropharyngeal lymphoid tissue. There is no hepatosplenomegaly.
CBC is normal except for findings of mild anemia.
A lymph node biopsy specimen shows replacement by a
monomorphous population of lymphoid cells that are twice the
size of normal lymphocytes, with enlarged nuclei and prominent
nucleoli. Immunohistochemical staining and flow cytometry
of the node indicates that most lymphoid cells are CD19+,
CD10+, CD3−, CD15−, and terminal deoxynucleotidyl transferase
negative (TdT−). A BCL6 gene mutation is present. Which of
the following is the most likely diagnosis?
A Acute lymphoblastic lymphoma
B Chronic lymphadenitis
C Diffuse large B-cell lymphoma
D Hodgkin lymphoma
E Small lymphocytic lymphoma
C Diffuse large B-cell lymphoma
Diffuse B cell lymphoma
30 A 62-year-old man has had fever and a 4-kg weight loss
over the past 6 months. On physical examination, his temperature
is 38.6° C. He has generalized nontender lymphadenopathy, and
the spleen tip is palpable. Laboratory studies show hemoglobin,
10.1 g/dL; hematocrit, 30.3%; platelet count, 140,000/mm3; and
WBC count, 24,500/mm3 with 10% segmented neutrophils, 1%
bands, 86% lymphocytes, and 3% monocytes. A cervical lymph
node biopsy specimen microscopically shows a nodular pattern
of small lymphoid cells. A bone marrow biopsy specimen shows
infiltrates of similar small cells having surface immunoglobulins
that are CD5+, but CD10−. Cytogenetic analysis indicates t(11;14)
in these cells. What is the most likely diagnosis?
A Acute lymphoblastic lymphoma
B Burkitt lymphoma
C Follicular lymphoma
D Mantle cell lymphoma
E Small lymphocytic lymphoma
D Mantle cell lymphoma
Mantle cell lymphoma
42 A 33-year-old man has experienced multiple nosebleeds
along with bleeding gums for the past month. On examination,
his temperature is 37.3° C. He has multiple cutaneous ecchymoses.
Laboratory studies show hemoglobin, 8.5 g/dL; hematocrit,
25.7%; platelet count, 13,000/mm3; and WBC count,
52,100/mm3 with 5% segmented neutrophils, 5% bands, 2%
myelocytes, 83% blasts, 3% lymphocytes, and 2% monocytes.
Examination of his peripheral blood smear shows the blasts
have delicate nuclear chromatin along with fine cytoplasmic
azurophilic granules. These blasts are CD33+. Which of the
following morphologic findings is most likely to be present on
his peripheral blood smear?
A Auer rods
B Döhle bodies
C Hairy projections
D Heinz bodies
E Sickle cells
F Toxic granulations
A Auer rods
AML
43 A 38-year-old man experiences sudden onset of a severe
headache. Physical examination shows no localizing neurologic
signs and no organomegaly. A stool sample is positive
for occult blood. Areas of purpura appear on the skin of his
extremities. Laboratory studies show hemoglobin of 9.6 g/dL,
hematocrit of 28.9%, platelet count of 16,400/mm3, and
WBC count of 75,000/mm3. The peripheral blood smear
has the appearance shown in the figure; schistocytes also
are seen. The plasma D-dimer level (fibrin degradation products),
prothrombin time, and partial thromboplastin time
all are elevated. Cytogenetic analysis of cells from a bone marrow
biopsy specimen is most likely to yield what karyotypic
abnormality?
A t(8;14)
B t(8;21)
C t(9;22)
D t(14;18)
E t(15;17)
E t(15;17)
Acute promyelocytic leukemia (M3)
47 In an experiment, cell samples are collected from the
bone marrow aspirates of patients who were diagnosed with
lymphoproliferative disorders. Cytogenetic analyses are performed
on these cells, and a subset of the cases is found to have
the BCR-ABL fusion gene from the reciprocal translocation
t(9;22)(q34;11). The presence of this gene results in increased
tyrosine kinase activity. Patients with which of the following
conditions are most likely to have this gene?
A Acute promyelocytic leukemia
B Chronic myelogenous leukemia
C Follicular lymphoma
D Hodgkin lymphoma, lymphocyte depletion type
E Multiple myeloma
B Chronic myelogenous leukemia
CML
49 A 60-year-old woman has had headaches and dizziness for
the past 5 weeks. She has been taking omeprazole for ulcers. On
physical examination, she is afebrile and normotensive, and her
face has a plethoric to cyanotic appearance. There is mild splenomegaly,
but no other abnormal findings. Laboratory studies
show hemoglobin, 21.7 g/dL; hematocrit, 65%; platelet count,
400,000/mm3; and WBC count, 30,000/mm3 with 85% polymorphonuclear
leukocytes, 10% lymphocytes, and 5% monocytes.
The peripheral blood smear shows abnormally large platelets
and nucleated RBCs. Which of the following is most characteristic
of the natural history of this patient’s disease?
A Development of a gastric non-Hodgkin lymphoma
B Increase in monoclonal serum immunoglobulin
C Marrow fibrosis with extramedullary hematopoiesis
D Spontaneous remissions and relapses without
treatment
E Transformation into acute B-lymphoblastic leukemia
C Marrow fibrosis with extramedullary hematopoiesis
Polycythemia vera (PCV)
50 A 45-year-old man has experienced a gradual weight
loss and weakness, anorexia, and easy fatigability for 9
months. Physical examination shows marked splenomegaly. CBC shows hemoglobin, 12.9 g/dL; hematocrit, 38.1%; MCV, 92 μm3; platelet count, 410,000/mm3; and WBC count,
168,000/mm3. The peripheral blood smear is depicted in the figure. Karyotypic analysis shows the Ph1 chromosome. The patient undergoes chemotherapy with imatinib mesylate (tyrosine kinase inhibitor). He remains in remission for 3 years and then begins to experience fatigue and an 8-kg weight loss. CBC shows hemoglobin, 10.5 g/dL; hematocrit, 30%; platelet count, 60,000/μL; and WBC count, 40,000/μL. Karyotypic analysis shows two Ph1 chromosomes and aneuploidy. Flow cytometric analysis of the peripheral blood shows CD19+,
CD10+, sIg−, and CD3− cells. Which of the following
complications of the initial disease did this patient develop
after therapy?
A Acute myeloblastic leukemia
B B-cell lymphoblastic leukemia
C Hairy cell leukemia
D Myelodysplastic syndrome
E Sézary syndrome
B B-cell lymphoblastic leukemia
CML
51 A 50-year-old man has had headache, dizziness, and
fatigue for the past 3 months. His friends have been commenting
about his increasingly ruddy complexion. He also has experienced
generalized and severe pruritus, particularly when
showering. He notes that his stools are dark. On physical examination,
he is afebrile, and his blood pressure is 165/95 mm Hg.
There is no hepatosplenomegaly or lymphadenopathy. A stool
sample is positive for occult blood. CBC shows hemoglobin,
22.3 g/dL; hematocrit, 67.1%; MCV, 94 μm3; platelet count,
453,000/mm3; and WBC count, 7800/mm3. What is the most
likely diagnosis?
A Chronic myelogenous leukemia
B Erythroleukemia
C Essential thrombocytosis
D Myelodysplastic syndrome
E Polycythemia vera
E
Polycythemia vera (PCV)
27 A 67-year-old man has had increasing weakness, fatigue, and weight loss over the past 5 months. He now has decreasing vision in both eyes and has headaches and dizziness. His hands are sensitive to cold. On physical examination, he has generalized lymphadenopathy and hepatosplenomegaly. Laboratory studies indicate a serum protein level of 15.5 g/dL and albumin concentration of 3.2 g/dL. A bone marrow biopsy is performed, and microscopic examination of the specimen
shows infiltration by numerous small plasmacytoid lymphoid cells with Russell bodies in the cytoplasm. Which of the following additional laboratory findings is most likely to be reported for this patient?
A Bence Jones proteinuria
B Hypercalcemia
C Karyotype with t(14;18) translocation
D Monoclonal IgM spike in serum
E WBC count of 255,000/mm3
D Monoclonal IgM spike in serum
Lymphoplamacytic lymphoma (waldenstrom macroglobulinema)
Hyperviscosity Visual distrubances Dizziness Headache Raynaud
48 A 63-year-old woman experiences a burning sensation
in her hands and feet. Two months ago, she had an episode
of swelling with tenderness in the right leg, followed by dyspnea
and right-sided chest pain. On physical examination, the
spleen and liver now appear to be enlarged. CBC shows hemoglobin,
13.3 g/dL; hematocrit, 40.1%; MCV, 91 μm3; platelet
count, 657,000/mm3; and WBC count, 17,400/mm3. The peripheral
blood smear shows abnormally large platelets. Which
of the following is the most likely diagnosis?
A Acute myelogenous leukemia
B Chronic myelogenous leukemia
C Essential thrombocytosis
D Myelofibrosis with myeloid metaplasia
E Polycythemia vera
C
Essential thrombocytosis
35 An 83-year-old man complains of worsening malaise
and fatigue over the past 5 months. On physical examination,
he is afebrile and normotensive. The spleen tip is palpable.
A CBC shows hemoglobin, 10.6 g/dL; hematocrit, 29.8%;
MCV, 92 μm3; platelet count, 95,000/mm3; and WBC count,
4900/mm3 with 63% segmented neutrophils, 7% bands, 2%
metamyelocytes, 1% myelocytes, 22% lymphocytes, 5% monocytes,
and 3 nucleated RBCs per 100 WBCs. The peripheral
blood smear shows occasional teardrop cells. An examination
of the bone marrow biopsy specimen and smear is most likely
to show which of the following findings?
A Erythroid hyperplasia
B Extensive fibrosis
C Fatty replacement
D Many megaloblasts
E Numerous myeloblasts
B
Myelofibrosis
Tear drop cells
52
A
Myeofibrosis
Waldenstrom Macroglobulinema
- proliferation
- associated with
- dont have
Monoclonal proliferation of IgM
Assoc w/
- Amyloidosis
- Hyperviscosity
No lytic bone lesions
Myeloproliferative neoplasma
3 types
mutation
Monclonal proliferation of mature myeloid cells
Types
- polycythemia vera
- essential thrombocytosis
- myelofibrosis
Mutation
- JAK2
JAK2 mutation in red cell precursor
Increased red cell mass
Decreased erythropoietin
Polycythemia vera
Red face Pruritis after hot shower Splenomegaly hyperviscosity of blood HA Red hands and feet
Polycythemia vera
Increased platelets
Low thrombopoietin
Essential thrombocytosis
Fibrosis and olbiteration of marrow space
tear drop
Myelofibrosis
Monoclonal Ab spike
MM
MGUS
Waldenstrom macroglobulinemia
MM urine analysis
No protein in urine
Monoclonal Ab spike on UPEP
A patient presents with hypertension, hypokalemia, metabolic alkalosis and low plasma renin.
Diagnosis?
Treatment
Primary hyperaldosteronism (Conn syndrome)
Spironolactone
Stain for carcinoma
Cytokeratin stain
Epithelial vs mesenchymal tumors
Epithelial
- adenoma
- papilloma
- carcinoma
Mesenchymal
- sarcoma
- oma
Liver metastasis
“Cancer Sometime Penetrates Benign Liver”
Colon Stomach Pancreas Breast Lung
Colon»_space; stomach > pancreas
Elevated LFTs Abdominal pain Hepatomegaly Ascites Jaundice
Brain Metastasis
“Lots of Bad Stuff Kills Glia”
Lung Breast Skin (melanoma) Kidney GI tract
Lung > breast > melanoma, colon, kidney
HA
Neurological deficits
Cognitive function
Seizures
Well circumscribed tumors at grey/white matter junctions
Bone Metastasis
“Permanently Relocated Tumors That Like Bone”
Prostate Renal cell cancer Testes Thyroid Lung Breast
Prostate, breast > lung, thyroid, kidney
Hypercalcemia of malignancy
Squamous cell lung cancer
Secretes PTHrP
Head and neck squamous cancers
Breast cancer
Renal cell carcinoma
Paraneoplastic of Small cell lung cancer
ACTH –> cushing syndrome
ADH –> SIADH
- hyponatremia
Lambert eaton syn
- antibodies against presynaptic calcium channel at NMJ
- weakness improve with use
Cerebellar degeneration
Psammoma bodies
Lamellated concentric calcific spheruloes
Rings in a tree
PSaMMoMa bodies
- Papillary thyroid cancer
- Serous papillary cystadenocarcinoma of the ovary
- Malignant mesothelioma
- Meningioma
What cancer is associated with Hashimoto thyroiditis
Marginal cell lymphoma
To which main two molecules is iron bound in human cells?
To which two main molecules is iron bound in blood?
Human cells
- Myoglobin
- Ferritin
Blood
- Hemoglobin
- Transferrin
Rb mutation
- type of mutation
- see in
- sporadic vs inherited
- Rb normal binds to
Tumor suppressor gene mutation
TWO mutations
Retinoblastoma
Osteosarcoma
White reflex in eye
60% sporadic (unilateral)
40% inherited (unilateral or bilateral)
E2F
Mutation seen in more than 50% of human cancers
p53
causes cell cycle arrest normally
Mutation in APC
- type mutation
- seen in
Tumor suppressor genes
Negative regulator of beta-catenin/WNT pathway
Familial adenomatous polyposis
Colon cancer
BRCA mutation
- type of mutation
Tumor suppressor genes
- DNA repair protein
BReast CAncer (only 3% have this mutation)
Ovarian cancer
DPC mutation
Tumor suppressor protein
Deleted in pancreatic cancer
DCC mutation
Tumor suppressor protein
Deleted in colon cancer
NF1 mutation
- type of mutation
- chromosome
- presentation
Tumor suppressor protein
- Neurofibromin (Ras GTPase activating protein)
NF type 1
Neurofibromas, cafe au lait spots
Chr 17
NF2 mutation
- type of mutation
- chromosome
- presentation
Tumor suppressor protein
- Merlin (schwannomin) protein
NF type 2
Bilateral acoustic schwannoma
chr 22
WT1 WT2 mutation on what chromosome
type of mutation
Tumor suppressor protein
chr 11
Von Hippel Lindau mutation on what chromosome
type of mutation
Tumor suppressor protein
Chr 3
Most common mutations
p53 and RAS
RAS mutation
oncogene mutation
1 mutated allele
K-RAS mutation
- type
- seen in
oncogene mutation
Colon
Lung
Pancreatic tumors
H-Ras mutation
- type
- seen in
oncogene mutation
Bladder and kidney tumors
N-RAS mutation
- type
- seen in
oncogene mutation
Melanomas
Hematologic malignancies
Follicular thyroid cancer
BCR-ABL
- type
- normal fxn
- what occurs
- seen in
oncogene mutation
- tyrosine kinase
ABL codes for tyrosine kinase
ABL translocated from 9 to 22
Philadelphia chromosome
CML
RET mutation
- type mutation
- associated with
oncogene mutation
- receptor tyrosine kinase
MEN 2A and 2B
- Pheochromocytoma
- Medullary thyroid cancer
Papillary carcinoma of thyroid
HER2/neu mutation
- type mutation
- seen in
oncogene mutation
- receptor tyrosine kinase
ERBB2
Breast cancer
Ovarian cancer
Gastric cancer
c-myc
- type mutation
- seen in
oncogene mutation
- transcription factor
burkitt lymphoma
L-myc
Lung tumors
N-myc
Neuroblastoma (adrenal medulla)
What is the most common urea cycle disorder
Ornithien transcarbamylase deficiency
Aflatoxins
Toxins produced by aspergillus mold
Causes mutation in p53
Nitrosamines
- found in
- assoc with
Found in smoked foods
Assoc w/
- Gastric cancer
- Squamous cell esophageal cancer
Arsenic causes
Lung cancer
Squamous cell skin cancer
angiosarcoma- Liver
Vinyl chloride causes
angiosarcoma- liver
Alkylating agents assoc with
Leukemia
Lymphoma
Benzene assoc with
Leukemia
Hodgkin lymphoma
Naphthalene causes
Transitional cell bladder cancer
HHV-8
Kaposi sarcoma
EBV associated iwth
Hodgkin lymphoma
(Reed-sternberg cells)
Burkitt lymphoma
(starry sky, 8;14)
Nasopharyngeal carcinoma
Streptococcus bovis assoc with
Colon cancer
Schistosoma haematobium assoc with
Squamous cell cancer of bladder
Clonorchis sinensis assoc with
Biliary cancer
Tuberous sclerosis associated with what neoplasms
Cardiac rhabdomyoma
Renal angiomyolipoma
Astrocytoma
Ionizing radiation associated with what neoplasms
AML
CML
Papillary thyroid cancer
What UV radiation most problematic
UVB
What is the RL enzyme in purine synthesis?
RL enzyme in pyrimidine synthesis?
Purine: Glutamine PRPP amidotransferase
Pyrimidine: Carbamoyl phosphate synthase 2
PSA tumor marker
Prostate cancer
CA-125
Ovarian cancer
Alkaline phosphatase
bone metastasis
Biliary disease
paget disease of bone
alpha-fetoprotein
hepatocellular carcinoma
Testicular tumors
CA 19-9
pancreatic cancer
CEA
Calcitonin
Chromogranin
Colon
Pancreatic cancer
Medullary thyroid cancer
(alone and with MEN2A, MEN2B)
Neuroendocrine tumors
S-100
Melanoma
Schwannoma
Tartrate-resistant acid phosphatase (TRAP)
Hairy cell leukemia
Which tumor marker would you use to monitor each?
- Hepatocellular carcinoma
- Ovarian cancer
- Pancreatic cancer
- Melanoma
- Colon cancer
- AFP
- CA-125
- CA 19-9, CEA
- S-100
- CEA
RL enzymes for each?
- Urea cycle
- Hexose monophosphate pathway
- Fatty acid synthesis
- Beta-oxidation of fatty acids
- Ketone body synthesis
- Cholesterol synthesis
- Bile acid synthesis
- Heme synthesis
- Carbamoyl phosphate synthetase I
- Glucose 6 phosphate dehydrogenase
- Acetyl CoA carboxylase
- Carnitine acyltransferase
- HMG CoA synthase
- HMG CoA reductase
- 7-alpha hydroxylase
- Aminolevulinate synthase
What are the irreversible enzymes involved in gluconeogenesis?
Pyruvate carboxylase (pyruvate –> oxaloacetate)
PEP carboxykinase
(oxaloacetate –> phosphoenolpyruvate)
Fructose 1,6 bisphosphatase
(Fructose 1,6- bisphosphate –> Fructose 6 phosphate)
Glucose 6 phosphate
(Glucose 6 phosphate –> glucose)
Enveloped viruses spread
Droplets perientrally or sexually
Non-enveloped viruses spread
Fecal oral spread
Non-enveloped RNA viruses
“my Real Heavy Picture of California was Ruined without an Envelope”
Reovirus
Hepevirus
Picornavirus
Calicivirus
Non-enveloped DNA viruses
“PaPa and Aunt Poly didnt have an Envelop”
Parvovirus
Papillomavirus
Adenovirus
Polyomavirus
DNA viruses typically replicate
In the nucleus
RNA viruses typically replicate
in the cytoplasm
DNA viruses that replicate in the cytoplasm
Smallpox virus
Molluscum contagiosum
RNA viruses that replicate in the nucleus
Influenza virus
Retroviruses
Viral recombination where two viruses exchange entire segment
- example
- only what
Viral reassortment
RNA viruses only
Influenza virus
When two different viruses infect same host a genes are exchanged from two different chromosomes
Viral recombination
When two viruses infect a cell and one is non-functional so other virus makes a functional protein that serves both viruses
Viral Complementation
When two viruses infect the same host and the progeny receive surface proteins from either parent
Phenotypic mixing
Ploidy of viruses
All RNA and DNA viruses are haploid
Except: retroviruses (2) of ssRNA
DNA viruses
- examples
- typical features
- exceptions
HAPPy HiPPo Dung
Herpesvirus Adenovirus Parvovirus Papillomavirus Hepadnavirus Polyomavirus Poxvirus DNA
Linear dsDNA
Icosahedral shape
Replicate in nucleus
Only parvoviridae (ssDNA)
Papillomarvirus (circular)
Polyomavirus (circular)
Hepadnavirus (circular)
RNA viral genomes
(+) stranded RNA viruses
I went to a RETRO TOGA party, where I drank FLAvored CORONA and ate HIPPIE CALIfornia PICkles
Retrovirus Togavirus Flavivirus Coronavirus Hepevirus Calicivirus Picornavirus
All ssRNA except reoviridae (dsRNA)
Negative-sense ssRNA
Not immediately translated
Can only be transcribed and not directly translated
Bring along viral transcriptase
Always Bring Polymerase Or Fail Replication
Arenaviruses Bunyaviruses Paramyxoviruses Orthomyxoviruses Filoviruses Rhabdoviruses
dsRNA brings along what
Polymerase
Live attenuated vaccine
“Attention Teachers” Please Vaccinate Small Beautiful Young Infants with MMR Regularly
Adenovirus Typhoid Polio (Oral) Varicella Small pox BCG Yellow fever Influena (intranasal) MMR Rotavirus
Killed vaccine
RIP Always
Rabies
Influenza (injection)
Polio (injectable)
Hepatitis A
Subunit vaccines
Use specific viral antigens to stimulate immune response
hepatitis B
HPV
Egg allergy
Yellow fever
Influenza
(MMR)
When should live virus vaccines be considered for HIV positive patients
All infants with HIV
- Rotavirus vaccine
CD4 count > 200
- MMR
- Varicella vaccine
Not recommended
- Live virus influenza vaccine
- Herpes zoster vaccine
What condition is suggested by each of the following
- Signet ring cells
- Nutmeg liver
- RBC casts in urine
- Gastric adenocarcinoma, lobular carcinoma in situ of breast
- Right sided heart failure and budd-chiari
- Acute glomerulonephritis
Infects spindle cells
HHV-8 Kaposi sarcoma associated herpesvirus (KSHV)
Temporal lobe encephalitis
Herpes simplex virus 1 (HSV-1)
Tzanck smear
Multinucleated giant cells positive
HSV-1, HSV-2, VZV
Low specificity
Low sensitivity
Intranuclear eosinophilic inclusions
Type A Cowdry bodies
HSV, VZV, CMV
EBV infects what cells
causes what
cell type seen
Infects B cells
Causes T cell response
Downey cells
- Foamy appearing basophilic cytoplasm
Foamy appearing cells with basophilic cytoplasm
Downey cells
T cells
EBV
Fever
Sorethroat
LAD of posterior cervical nodes
Splenomegaly
(+) monospot test
Infectious mononucleosis
EBV
Ab against antigens found on horse, sheep and beef RBCs
Monospot test
Detects heterophiles
EBV
Heterophile (-) mononucleosis
CMV infection
Acute HIV
Owl eye nuclear inclusions
CMV
Retinitis blind within days
CMV w/ AIDS
HIgh fever (102) 3-5 days
Fever breaks
Maculopapular rash all over body
Seizures
Roseola
Sixth disease
Human Herpes virus -6
What group of patients is prone to esopahgitis caused by CMV
HIV patients (CD4 < 50)
Hypoglycmeia
Jaundice
Cirrhosis
Fructose intolerance
Child with bright red rash on cheeks
Slap cheek rash Erythema infectiosum (fifth disease)
Parvovirus B19
Upper respiratory infection
Then conjunctivitis
Diarrhea
Adenovirus
dsDNA virus
Variola poxvirus vs vaccinia pox virus
Variola poxvirus
- smallpox
Vaccinia poxvirus
- cowpox
Flesh colored dome shaped lesions with central dimple (umbilication)
Molluscum contagiosum
In immunocompetent will resolve in less than a year
Demyelination of CNA due to destruction of oligodendrocytes
AIDS
Progressive
Visial symptoms
Progressive Multifocal leukoencephalopathy
JC virus
POlyomavirus
Only Hepatitis virus dsDNA
Hepatitis B virus
Hepatitis B virus is what type of virus
Hepadnavirus
Hepatitis B virus replication
dsDNA virus
Partially double-stranded circular DNA enter nucleus
Host polymerase makes RNA intermediate from dNA
Viral reverse transcriptase makes DNA from RNA intermediate
Hides in sensory ganglia of S2 S3
Hides in trigeminal ganglia
Hides in dorsal root ganglia
HSV-2
HSV-1
VZV
Opacities seen on X ray on both sides of carina
Bilateral hilar lymphadenopathy
Sarcoidosis
Common cold
Rhinovirus
Coronavirus
Severe diarrhea and vomiting Winter months Daycare center Non-enveloped dsRNA virus
Rotavirus
type of reovirus
Western US/ canada
Hiker, Fisherman, camping
Flu- like
Coltivirus
(type of reovirus)
Self limiting
Types of picornaviruses
Enterovirus
- Poliovirus
- Coxsackievirus
- Echovirus
- Hepatitis A virus
Rhinovirus
Types of enteroviruses
Enterovirus falls under Picornaviruses
Spread through enteric system
4 types
- Poliovirus
- Coxsackievirus
- Echovirus
- Hepatitis A virus
Poliovirus
Infects grey matter of the anterior horn of the spinal cord and motor neurons of the pons of the medulla
Causes paralysis
Aseptic meningitis
Myocarditis
URIs
Summer
-Diagnosis?
Echovirus
PCR of CSF
Hand foot and mouth disease
Coxsackievirus
Most common cause of viral myocarditis in US
Coxsackievirus
Dilation of all chambers Dyspnea Chest pain Fever Arrhythmias
Mouth blisters, fever
herpangina
Coxsackievirus
Coxsackievirus can cause
Myocarditis Aseptic meningitis Pericarditis herpangina (blisters mouth and fever) Hand, foot and mouth disease Febrile pharngitis
Picornavirus that is not an enterovirus
Rhinovirus
Common cold
Vomiting and diarrhea
Cruise ship
Norovirus (caliciviruses)
Fecal oral route
Types of flaviviruses
Yellow fever
Dengue fever
West nile virus
St. Louis Encephalitis virus
Most are arboviruses
(spread by arthropod)
High fever, HA Epistaxis Gum bleeding petechial and purpura Black vomit Jaundice Africa
Spread by?
Yellow Fever
Aedes mosquitoes
Liver damage
Fever
Severe musculoskeletal pain
Retro-orbital headache
Spread by?
Can get?
Test?
Dengue fever
Mosquito
Hemorrhagic fever
Tourniquet test
- field test for hemorrhagic fever
- BP inflated leave 5 min
- Excess petechiae
Headache Malaise Backpain Myalgia Anorexia Alteration in consciousness Neck stiffness
West Nile virus (WNV)
Mosquito
Serology for IgM anti-WNV antibodies
Tx supportive
A 26-year-old woman has headaches for 4 weeks
along with increasing malaise. Physical examination yields
no remarkable findings. CT scan of the head shows no
abnormalities. A lumbar puncture yields clear, colorless CSF
with a normal opening pressure. Laboratory analysis of the
CSF shows a normal glucose concentration and a minimally
increased protein level. A few lymphocytes are present,
but there are no neutrophils. A Gram stain and India ink
preparation of the CSF are negative. Her condition gradually
improves over the next 6 months. Serum serologic tests are
most likely to show an elevated titer of antibodies to which
of the following infectious agents?
A Cryptococcus neoformans
B Echovirus
C Listeria monocytogenes
D Neisseria meningitidis
E Toxoplasma gondii
B. Echovirus
Acute lymphocytic meningitis
West nile
Echovirus
Togaviruses
Rubella virus
Fever Lymphadenopathy
Arthralgia
Macuopapular rash
Rubella or german measles
Congenital rubella
Cardiac defects
- PDA
- Pulmonic stenosis
Cataracts
Deafness
11 A 6-year-old girl has a blotchy, reddish-brown rash
on her face, trunk, and proximal extremities that developed
over the course of 3 days. On physical examination, she has
0.2-cm to 0.5-cm ulcerated lesions on the oral cavity mucosa
and generalized tender lymphadenopathy. A cough with
minimal sputum production becomes progressively worse
over the next 3 days. Which of the following viruses is most
likely to produce these findings?
A Epstein-Barr
B Mumps
C Rubella
D Rubeola
E Varicella zoster
D Rubeola
Measles (rubeola)
Rash
Koplik spots
Rubella: german measles, is a much milder infection than rubeola
7 term infant has initial Apgar scores of 8 and 10 at 1
and 5 minutes. On auscultation of the chest, a heart murmur
is audible. There is hepatosplenomegaly. Cataracts of the crystalline
lens are noted. The infant is at the 30th percentile for
height and weight. Echocardiography shows a patent ductus
arteriosus. Which of the following events is the most likely
risk factor for the findings in this infant?
A Congenital rubella infection
B Dietary folate deficiency
C Dispermy at conception
D Erythroblastosis fetalis
E Maternal thalidomide use
F Paternal meiotic nondisjunction
A
Rubella in first trimester
38 A family who recently emigrated from Romania
brings their 7-year-old child to the pediatrician
with complaints of conjunctivitis and periorbital
swelling. The child has had coughing
with a runny nose and high fever for 3 days.
Small lesions with blue-white centers are seen
in his oral cavity. Which of the following is the
most likely cause of this child’s symptoms?
(A) Diphtheria
(B) Pertussis
(C) Roseola
(D) Rubella
(E) Rubeola
E
Rubeola
Retroviruses
Use reverse transcriptase
HIV
Human T cell Luekemia virus (HTLV)
What is the number one cause of fatal infantile gastroenteritis
Rotavirus
Posterior cervical adenopathy
EBV mononucleosis
Cat scratch disease (bartonella)
Acute otitis media
Avian influenza
H5N1
Spread only from bird to human
60% mortality
Severe rapidly progressive couse
Fever cough myalgias
diarrhea, pancytopenia
Tx: Oseltamivir
Swine flu
H1N1
Two swine strain
One human strain
One avian strain
Flu and GI symptoms
Tx: Oseltamivir or zanamivir
Influenza virus
- type of virus
- description of virus
- two key features
Orthomyxoviruses
Enveloped ssRNA
Hemagglutinin
- viral attachment to host cell
Neuraminidase
- release progeny virions
Barking seal cough child
Croup
Parainfluenza virus
- enveloped
Steeple sign
Croup
Parainfluenza virus
- enveloped
Winter months viruses
Influenza
Rotavirus
RSV
Summer months enterovirus
Poliovirus
Echovirus
Coxsackievirus
Summer months arbovirus
West Nile virus
Bronchiolitis
Child
Pneumonia in child
Infection of bronchioles
RSV
Primary cause of penumonia in children
RSV
RSV virus has what
Transmembrane protein called Fusion protein (F protein)
This allows infected cells to bond to near by uninfected cells
Multinucleated giant cells
55 A 3-year-old boy has had a cough, headache, and slight
fever for 5 days. He is now having increasing respiratory difficulty.
On physical examination, his temperature is 37.8° C,
pulse is 81/min, respirations are 25/min, and blood pressure
is 90/55 mm Hg. On auscultation, there are inspiratory crackles,
but no dullness to percussion or tympany. Respiratory
syncytial virus is isolated from a sputum sample. Which of
the following chest radiographic patterns is most likely to be
present?
A Hilar lymphadenopathy
B Hyperinflation
C Interstitial infiltrates
D Lobar consolidation
E Pleural effusions
F Upper lobe cavitation
C Interstitial infiltrates
RSV
Paramyxoviruses
RSV
Parainfluenza virus
Rubeola virus (measles)
Mumps
Runny nose
cough
Conjunctivitis
Blue grey specks on buccal mucosa surround by base of red
Wide spread maculopapular rash that started on head and spread
Measles
Enveloped
Koplik spots
Parotits
Orchitis
Meningitis
Mumps enveloped
Inflammation of parotid gland
Viral meningitis
Coxsackievirus
Echovirus
Enterovirus
Mumps virus
Negri bodies Fever Nausea vomiting Strange behavior Hallucinations Hydrophobia Coma Death
Rabies virus
(Rhabdovirus)
Enveloped RNA
Eosinophilic cytoplasmic inclusions that contain viral nucleocapsids
Negri bodies
Rabies
Bullet shaped capsid
Rabies
Fever
Progressive pulmonary edema
Respiratory failure
Exposure to mouse urine
Hantavirus
A 27-year-old man dies of acute respiratory distress
syndrome 1 day after presenting to the
hospital with shortness of breath and a fever of
38° C (100.4° F). On the second hospital day,
he developed extreme pulmonary edema and
hypotension before he died. His family says
that he had recently gone hiking and caving in
an area known to be heavily populated with rodents.
Which of the following is the most likely
cause of death?
(A) Dengue virus
(B) Ebola virus
(C) Hantavirus
(D) Marburg virus
(E) Rhabdovirus
C. Hantavirus
Illnesses spread through animal urine
Hantavirus
Lassa virus
LCM virus
Leptospirosis
Fever HA myalgias Followed by vomiting and diarrhea Multiorgan failure Shock Death
Ebola virus
A patient present with fever, vomiting and diarrhea. She was in Sierra Leone two weeks visiting family. What viral infection? Type of isolation
Ebola
Contact and droplet precautions
Viral proteins of HIV
Gp120
Gp41
Gp120
Grabs onto CD4 surface receptor on T cells and macrophages
Once connected, changes shape and allows it to bind to coreceptor (CCR5 or CXCR4)
Tropsim
Which coreceptor HIV uses to enter cell
only CXCR4: X4 viruses
Only CCR5: R5 viruses
Both : dual tropism
GP41
Fusion and entry into host cells
Three main structural genes in HIV genoma
Gag: encodes p24 capsid protein
Env: gp120 and gp41
Pol: codes for reverse transcriptase
Diagnosis of HIV check
P24 antigen adn HIV antibodies
Viral load (PCR test)
AIDS diagnosis
CD4 < 200
< 14% lymphocytes are Cd4
AIDs defining condition
- Pneumocystis jirovecii pneumonia
Ring enhancing lesions
HIV associated Primary CNS lymphoma
(solitary lesion)
Toxoplasmosis
(multiple lesions)
HIV < 200 opportunistic infections
Pneumocystis jirovecii pneumonia
HIV < 100 opportunistic infections
Histoplasmosis capsulatum
Candida albicans
HIV < 50 opportunistic infections
Mycobacterium tuberculosis
Mycobacterium avium complex
CMV retinitis
Hepatosplenomegaly
Fever
Cough
CD4 < 150
Histoplasmosis capsulatum
Chronic watery diarrhea
HIV patient
diagnosis
Cryptosporidium spp. (c.parvum)
Oocytes on modified acid-fast stain of stool turns bright pink or red
HIV patient covered in what look likes cherry angiomas
Bacillary angiomatosis
Bartonella henselae
What four molds are considered dermatophytes (fungal species that invade superficial skin)
Trichophyton
Microsporum
Epidermophyton
Malassezia furfur
Diaper rash
Satellite lesions
Candida albicans
Shiny skin or eroded
Blood culture
Germ tubes have small projections on side of cell
Candida albicans
Narrow based budding yeast
Cryptococcal neoformans
India ink
Clear circle
Cryptococcal neoformatns
Soap bubble lesion on imaging
Cryptococcal meningoencephalitis
Silver stain
Ground glass appearance of interstital infiltrates
Pneumocystis jirovecii (PCP)
Narrow septate hyphae that branch at acute angles (45 degrees)
Aspergillus fumigatus
Broad irregularly shaped, nonseptate hyphae branching at right angles (90 degrees)
Mucor and Rhizopus
Facial pain HA Large necrotic lesion, black escar Blindness CN deficits
Rhinocerebral mucomycosis
Most common type of dermatophytes with animal reservoir
Microsporium (dog or cat)
Hypopigmented or hyperpigmented lesion on body
Scaling plaque
Yeast
Tinea versicolor
Malassezia furfur
KOH prep spaghetti and meatball appearance
Tinea versicolor
Malassezia furfur
What is associated iwth each clue
- Cat scratch
- Cat bite
- Cat feces
- Puppy feces
- Animal urine
- Bartonella henselae
- Pasteurella multocida
- Toxoplasma
- Yersinia enterocolitica, campylobacter jejuni
- Leptospira, hantavirus
Leptin on hypothalamus
Inhibits lateral area and stimulates ventromedial area of hypothalamus
= satiety
Organisms associated with birds
Histoplasma capsulatum Cryptococcus neoformans Chlamydophilia psittaci H5N1 influenza West Nile virus
Mississippi ohio river valley
Bird and bat droppings
Spelunkers
- Imaging
- what happens to it
Histoplasma capsulatum
Enters through lung
Engulfed by macrophages
Hyphae and spores on imaging
Macrophage filled w/ 100 spores
Mississippi and ohio river basins
Thick refractile wall around yeast
broad based budding
Blastomyces dermatitidis
Granulomatous nodules
Southwestern U.S
Mexico
Pneumonia
Spherule
-filled with endospores
Coccidioides immitis
A 46-year-old man from northern Mexico has had fever,
nonproductive cough, and weight loss for 2 months. On examination
his temperature is 37.5 ° C. A chest radiograph shows
a miliary pattern of small nodules in all lung fields. Bronchoalveolar
lavage is performed and microscopic examination of
the fluid shows organisms averaging 50 microns in diameter
with thick walls and filled with endospores. Which of the following
infections is he most likely to have?
A Blastomycosis
B Coccidioidomycosis
C Histoplasmosis
D Mycobacteriosis
E Nocardiosis
F Paracoccidioidomycosis
B. Coccidioidomycosis
Pneumonia
Granulomatos changes in mucous membranes
Captain wheel
Latin america
Paracoccidioides brasiliensis
Paracocci parasails with a captains wheel all the way to Latin america
Gardner
Dimorphic fungus
Pustule on puncture site
Nodules follow draining lymphatics
Tx
Sporothrix schenckii
Tx: Itraconazole (first line)
potassium iodine
Mold form contains barrel shaped arthroconidia
Coccidioides immitis
Associated iwth dust storms
Coccidioides immitis
Multiple budding of yeast form
Paracoccidioides brasillensis
Councilman bodies
Apoptotic liver cells
Viral hepatits
yellow fever
Acute fatty foul smelling diarrhea
Abdominal bloating
- Diagnosis
Tx
Giardia lamblia
Pear-shaped trophozoites or cysts in stool
Metronidazole
Tinidazole
Pear-shaped trophozoites
Giardia lamblia
Bloody diarrhea
Flask shaped ulcers
RUQ pain
- type organism
- transmittered
- diagnosis
- tx
Entamoeba histolytica
Liver abscesses
Fecal-oral route
- eating food or water contaminated with feces that contain cysts
Trophozoites or cysts in stool
Treatment
- trophozoites= metronidazole or tinidazole
- cysts= iodoquinol or paromomycin
Foul smelling vaginal discharge
Motile
-transmission
- wet mount
- vaginal pH
- tx
-
Trichomonas vaginalis
Sexual transmission
Pear shaped appearance
Increase vaginal pH
Metronidazole
Ring enhancing lesions in brain
Toxoplasma gondii
Chorioretinitis
Hydrocephalus
Intracranial calcifications
Toxoplasma gondii
Toxoplasma gondii acquired how
Cat feces or litter
Eating cyst in infected meat
Rapidly fatal meningoencephaltiis
Swimming
Naegleria fowleri
Swimming in freshwater lakes
Enters nose passes through cribriform plate
A 40-year-old man goes on a camping vacation
with his family. One day after swimming in a
freshwater lake near the camp site, he develops
nausea and vomiting and starts to behave irrationally.
His family takes him to the emergency
department, where blood samples are taken
and a spinal tap is performed. He is diagnosed
with a rapidly progressing meningoencephalitis
and dies shortly thereafter. Which of the following
protozoa was most likely the cause of
the man’s illness?
(A) Cryptosporidium species
(B) Entamoeba histolytica
(C) Leishmania donovani
(D) Naegleria fowleri
(E) Plasmodium falciparum
(D) Naegleria fowleri
55 A 9-year-old child who is living in a mud hut in Paraguay
has a sore persisting on her face for 4 days. Physical examination
shows an indurated area of erythema and swelling just
lateral to the left eye, accompanied by posterior cervical lymphadenopathy.
She has unilateral painless edema of the palpebrae
and periocular tissues. Two days later, she has malaise, fever,
anorexia, and edema of the face and lower extremities. On
physical examination 1 week later, there is hepatosplenomegaly
and generalized lymphadenopathy. Which of the following
pathologic findings is most likely to develop in this patient?
A Cerebral abscesses
B Chronic arthritis
C Dilated cardiomyopathy
D Meningitis
E Mucocutaneous ulcers
F Paranasal bony destruction
C Dilated cardiomyopathy
Trypanosoma cruzi
Trypanosoma brucei spp
African sleeping sickness
tsetse fly
Fever
Enlarged LN
Sleepiness
Encephaltiis
Coma and death
Blood smear: long whispy organisms in blood
Early: Suramin
CNS involved: Melarsoprol
Dilated cardiomyopathy
Megesophagus
Megacolon
Trypanosoma cruzi
Chagas disease
Reduviid bug
- painless bit
- Feces scrated into skin
Benznidazole
Nifurtimox
Spiking fevers
Hepatosplenomegaly
Pancytopenia
- transmission
- diagnosis
- tx
Leishmania donovani
Visceral leishmaniasis
Sandfly
Amastigotes inside macrophages
Liposomal amphotericin B
Ulcerating papules that are slow to heal
Leishmania donovani
- Cutaneous leishmaniasis
Sandyfly
Sodium stibogluconate
Cyclic fever
Headache
Anemia
Splenomegaly
Malaria
Plasmodium species
Mosquito
Malaria fever due to
RBCs rupture and release merozoites
Malaria that fever spikes every 48 hrs
Every 72 hrs
48 hr
- P. ovale
- P. vivax
72 hr
- P. malariae
Malaria
- subtype
- tx
- Diagnosis
Plasmodium species
P. vivax and P. ovale
- dormant infection in liver
Tx primaquine
P. falciparum - most severe - no dormant form - sequestration of RBCs --> occlusion of small vessels Tx: Chloroquine
Blood smear
- Merozoites
- Trophozoite= diamond ring
- Gametocytes: banana shaped
Two ring forms inside one erythrocyte
Trophozoite form
Babesia Microti
Maltese cross
inside RBC
merozoites
Babesia Microti
Babesia Microti
- symptoms
- blood smear
- transmission
- tx
Fever
Hemolytic anemia
Two rings inside RBC
Maltese cross
Ixodes tick
coinfection w/ lyme disease
Tx
Quinine + Clindamycin
Names of following stages of malaria life cycle
- Looks like diamond ring
- Ruptures the cell host
- Replicating intracellularly
- Form injected from the anopheles mosquito
- banana shaped
- Early trophozoite
- Merozoite
- Schizont
- Sporozoite
- Gametocyte
Ingest helminths
“EAT”
Enterobius vermicularis
Ascaris lumbricoides
Trichinella spiralis
Penetrating helminths
“Sand”
Stronglyoides
Ancylostoma
Necator
D
Worm lays eggs at anus
tx
Enterobius vermicularis
Nematode (round worm)
Benzimidazoles
- Albendazole
- mebendazole
Pyrantel pamoate
Giant round worm
Eosinophilic pneumonitis
- diagnosis
- tx
Ascaris lumbricoides
Ingest eggs Hatch in intestines Release larvae penetrate bowel --> lungs Migrate up trachea and swallowed Mature worms in intestine
Eggs released in stool
Benzimidazoles
- Albendazole
- mebendazole
Pyrantel pamoate
Myositis
Fever
Eosinophilia
Periorbital edema
- acquired
- diagnosis
- tx
Trichinella spiralis
Undercooked meat
GI –> muscles
Muscle biopsy: cysts with larvae in muscle tissues
Bendzimidazoles
A 28-year-old woman from rural Guyana with a history
of rheumatoid arthritis develops painful swelling of her
hands and feet. She is treated with corticosteroid therapy.
A month later, she develops profuse, watery diarrhea along
with fever and cough. On examination, she has a temperature
of 37.3° C. Laboratory studies show WBC count, 12,900/
mm3; and the WBC differential count shows 57% segmented
neutrophils, 5% bands, 16% lymphocytes, 8% monocytes,
and 14% eosinophils. Microscopic examination of a stool
specimen shows ova and small rhabditoid larvae. Similar
larvae are present in a sputum specimen. Which of the following
infectious diseases is most likely to produce these
findings?
A Cysticercosis
B Onchocerciasis
C Schistosomiasis
D Strongyloidiasis
E Trichinosis
D. Strongyloidiasis
Rhabditiform larvae in feces
tx
Strongyloides
Threadworm
Ivermectin
Albendazole
Wound on feet
Anemia
Abdominal discomfort
tx
Ancylostoma
Necator
Hook worms
Benzimidazoles
- Albendazole
- mebendazole
Pyrantel pamoate
Taenia solium
- transmission
- symptoms
- tx
Cestodes (tapoworms)
Ingestion of alrvae in undercooked port
- GI tract infection by adult worm
Ingestion of eggs in contaminated food or water
- brain filled w/ cysts
Tx
Albendazole
Praziquentel
Dexamethaone: keep CNS symptoms from getting worse
Cestodes
Tape worms
Taenia solium
Diphyllobothrium latum
Echinococcus granulosus
Brain filled with cysts
Seizures
Taenia solium
Ingestion of eggs in contaminated food
Giant limbs
- type
- transmitted
- tx
Wuchereria bancrofti
Helminth, neomatoid
Round worm in GI
Mosquitoes
Migrate to lymphatics
Elephantiasis of limbs
Hydrocele of scrotum
Tx
Diethylcarbamazine
Raw fish
Megaloblastic anemia
-def
tx
Diphyllobothrium latum
B12 deficiency
Praziquantel
Hydatid cyst lesion in liver
RUQ pain
Well circumscribed circular lesion
- transmitted
- can find where in body
- symptom
- tx
Echinococcus granulosus
dog feces
Form mature larval cysts in liver and lungs
Anaphylaxis
Surgical removal of cysts
A 23-year-old man presents to the physician
with abdominal distention and tenderness with
no vomiting or diarrhea. Physical examination
shows hepatosplenomegaly. Bowel sounds are
normal. On questioning, the patient says that
he traveled to eastern South America 1 year
ago. Several weeks after returning from his trip,
he remembers having fever, diarrhea, weight
loss, and “funny looking stools.” Ultrasonography
shows ascites and hepatic periportal fi brosis.
Which of the following is most likely
responsible for this patient’s present symptoms?
(A) Appendicitis
(B) Bowel obstruction
(C) Enterocolitis
(D) Portal hypertension
(E) Ruptured viscus
D. Portal hypertension
Schistosoma mansoni
A 29-year-old man has had hematuria for the past
month. On physical examination, he is afebrile. There is diffuse
lower abdominal tenderness, but no palpable masses. An
abdominal radiograph shows a small bladder outlined by a
rim of calcification. Cystoscopy is performed, and the entire
bladder mucosa is erythematous and granular. Biopsy samples
are taken. Which of the following histologic findings is
most likely to be seen in these samples?
A Acid-fast bacilli of Mycobacterium avium complex
B Eggs of Schistosoma haematobium
C Larvae of Trichinella spiralis
D Migrating Ascaris lumbricoides
E Taenia solium cysts
B. Eggs of schistosoma haematobium
Deals with snails
Schistosoma
Portal HTN
Splenomegaly
Egyptian immigrant
tx
Schistosoma
- blood fluke
Praziquantel
Chronic bronchitis
Hemoptysis
acquired
-t x
Paragonimus westermani
Adult fluke in lung
Undercooked crab meat
Praziquantel
Pigmented gallstones
Cholangiocarcinoma
- transmission
- lives
- Tx
Clonorchis sinensis
- liver fluke
undercooked fish
Lives in biliary tract
Praziquantel
Albendazole
Swimmers itch
Schistosoma
Fluke associated iwth hematuria and bladder cancer
Schistosoma haematobium
Burns all over the body what will occur over the 7 day?
Increased metabolic rate
Not
- Increased extracellular volume
- Not increase in serum cholesterol concentration
- Not loss of B vitamins in skin
Testicular tumor with friend egg appearance
Seminoma
Germ cell tumor
Umbilical cord compression of infant, monitoring shows a normal fetal heart rate of 150/ min with variable spontaneous decelerations to 110/min. Why the decrease in fetal heart rate
Increased fetal systemic vascular resistance
Compressing vessel, decreases radius increase in resistance
Cause reflex bradycardia
20 yr history of T1D uses insulin
why hypoglycemia
Impaired release of glucagon
Subscapularis does what
internal rotation
Parathyroid effects on parts of kidney
Increase reabsorption of Ca in distal convoluted tubule
Decreased reabsorption of phosphate in proximal convoluted tubule
Increase 1,25 OH2 D3 production by stimulating kidney in 1alpha-hydroxylase in PCT
Transfusion reactions
Type II hypersensitivity
Bone conduction > Air conduction
Conductive hearing loss
Otosclerossi
Pregnancy, pituitary enlargement
Lactotroph hyperplasia due to estrogen increase
Lupus
- type of rxn
- deficiency of
type II hypersensitivity
C1q, C4, C2
Genetic component to hypertrophic obstructive cardiomyopathy
Mutations in sarcometric proteins
- myosin binding protein C
- beta-myosin heavy chains
Papilledema
increased
HTN
Increased angiotensin
Primary adrenal insufficiency labs
Hyponatremia
Hyperkalemia
Metabolic acidosis
Hyperkalemia leads to K entering all cells (via H/K exchanger in exchange for H exiting cells)
Fixed split S2
Systolic murmur at left sternal border
Atrial septal defect
Panic attack what will the labs show
Hyperventilating
Decrease PCO2
Respiratory alkalosis
Bioavailability on graph
area under the curve
Inject 5% saline what changes
Hypertonic into extracellular space
water from intracellular into extracellular
Decrease IC vol
Increase IC osm
Increase EC vol
Inc osm vol
Hypotonic saline
Isotonic saline
Hypertonic saline
.45% saline= hypo
.9%= isotonic
3%= hypertonic
Explains impaired action potential in axons of people with MS
Increased axonal capacitance
Prostate cancer spread to
by means of
Spine
Prostatic venous plexus to vertebral venous plexus
Mechanical ventilation on
- peak inspiratory alveolar
- end-tidal alveolar
- peak inspiratory intrapleural
- end-tidal intrapleursal
Positive on all
Pap smear columnar cells seen where?
Cervical canal
Doesn’t reach endometirum
Histology of female parts
Labia major= SS keratinized
Labia minor= SS nonkeratinized
Vagina= ss nonkeratinized Ectocervix= ss nonkeratinized
Endocervix= simple columnar
Body uterus= simple columnar
Fluoxetine affects neurons arising from
SSRI
From Raphe nucleus
NE is from
Locus cereuleus
GABA from
Nucleus accumbens
Dopamine from
Ventral tegmentum SNc
Acetylcholine from
Basal nucleus of Meynert
Erythematous scaly rings with central clearing
From pet
Tinea corporis
Leukomoid vs CML
Leukomoid
- high alkaline phosphate (LAP)
CML
- low leukocyte alkaline phospahtase
Strawberry hemangioma
Benign capillary hemangioma of infancty
Renal artery aneurysn due to
Fibromuscular dysplasia
Silicosis, asbestosis, coal workers lung
FEV1/FVC
FVC
Diffusion capacity of lung for carbon monoxide
Interstitial lung diseases
FEV1/FVC: normal
FVC: Decreased
Diffusing capacity: Decreased
(short swallow breaths)
White plaque on side of tongue
what happens if dont tx
Hairy leukoplakia
EBV
Progress into submucosa
Black escar nose
Mucor
Ixodes deer tick
Borrelia burgdorferi
Anaplasma
Babesia
Part of eye with least impact on vision
Iris
Fever Diarrhea Splenomegaly Muscle wasting Pancytopenia
Bitten sand fly
Leishmania spp
What shows up right after a burn with a blister
Histamine
Phototherapy does what
Increased conversion of bilirubin to water soluble isomers
18 month old failure to thrive and frequent wet diapers. 3rd percentile for length and weight. Physical examination shows dehydration, decreased muscle tone, and bowing of legs. Slit lamp examination shows crystals in corneas. Hypophosphatemia, hypokalemia, nonanion gap metabolic acidosis. pH of 5, glucosuria, phorphaturia, and generalized aminoaciduria. Cuase of metabolic acidosis in this patient
Decreased sodium bicarbonate reabsorption in the proximal tubule
Bulimia Nervosa
- potassium
- chloride
- bicarbonate
- acidosis/ alkalosis
K
- decreased
Chloride
- increased
Bicarbonate
- decreased
Alkalosis
New born 2 weeks old, yellow skin for 7 days. At birth, lethargic and hypoglycemia. Vomits at feedings. PE shows jaundice. There is no glucosuria but reducing substances are detected in the urine. Direct bilirubin concentration is increased. An assay for what will give a diagnosis
Galactose-1-phosphate uridyltransferase
Normoblast
Megakaryocyte
Normoblst: production of RBC
Megakaryocyte: production of platelet
Leukotrienes do what
LTC4
LTD4
LTE4
Increase bronchial tone
LBT4
- increase neutrophil chemotaxis
Prostacyclin do what
Decrease platelet aggregation
Decrease vascular tone
Prostaglandins do what
Decrease vascular tone
Increase uterine tone
Thromboxane do what
Increase platelet aggregation
Increased vascular tone
Small cell lung cancer
- secretes
tx
SIADH
Demeclocycline
Split S1. First component of sound
Closure of mitral valve
Cerebellar hemisphere lesion on right see deficits on
Right
Lateral eye movement
CN VI
Pons
Stellate gangion stimulation
heart rate
Chronic renal failure
- Prosphate
- Ca
- PTH
Phosphate increase
Ca decrease
Parathyroid increase
Crash crash
Fractures and lacerations
Tachypnea, tachycardia and cyanosis
Diffuse consolidation of both lungs
what is seen on autopsy
Hyaline membranes
acute respiratory distress
Leukocyte differential
WBC
no T cell or B cell
How are integral membranes anchored
Extensive hydrophobic interactions between the amino acid side chain of the protein and the membrane phospholipid tails
Bronze diabetes
Hemochromatosis
HFE gene mutation chr 6
HLA-A3
Increased ferritin
Increased iron
Decreased TIBC
Increased transferrin saturation
Microcytic anemia types
Thalassemia
Anemia of chornic disease
Iron deficiency
Lead poisoning
TAIL
Microcytic anemia
Asain
Alpha thalassemia
Most common lung cancer
adenocarcinoma
Disease form bed bugs
Staph aureus
Erectile dysfunction nerve
Cavernous n.
Inferior hypogastric form
pelvic splanchnic
Sperm missing tails
Primary ciliary dyskinesia (PCD)
AR
Bronchiectasis another symptoms
Situs inversus
E coli makes many proteins how
mRNA contains sequence for many proteins
Scratches
Vetarianian
Parrot
Tender regional lymphadenopathy
Bartonella henselae
Bartonella henselae can cause what in immunocompromised
Bacillary angiomatosis
Red-purple papular skin lesions
Pulmonary embolism does what to pH, PaO2, PaCO2, Serum HCO3
pH increase
PaO2 decrease
PaCO2 decrease
Serum HCO3 Normal
PE occludes parenchyma resulting in increased dead space ventilation
Hyperventilation –> hypocapnia and respiratory alkalosis
Acute so no bicarb involvement yet
Fever myalgias, malaise, and progressive fatigue over 2 week period
No sore throat
Splenomegaly
No Lad or jaundice
Fails to agglutinate horse erythrocytes
Mono
(normally EBV0
but since no agglutination
CMV
Regulates glucose homeostasis during prolonged fasting by altering transcription of many key enzymes
Cortisol (cytoplasm) Growth hormone ( membrane-bound)
Splenomegaly on histology
Red pulp expansion
Additional thing to check if alkalosis
Urine Cl
- checks vomiting
- checks diuretic
Noscomal infections
Coag neg staph
Staph aureus
Enterococci
Candida
Increase in use of what has increased staph noscomal infections
Intravascular catheters
Strongest factor for risk of completed suicide
Past suicide attempt
Arthritis
Drug for treat causes
Mouth ulcers
Elevates AST ALT
Methotrexate
Most infections that arise after chemotherapy are from
Patients own endogenous bacterial flora
Tetralogy of fallot squatting does what
Ventricular septal defect
Overriding aorta
Increases systemic vascular resistance
Increase SVR causes a higher proportion of right ventricular output into pulmonary circulation rather than into left ventricle
Foot drop
Loss sensation on dorsum of foot
Nerve compressed where
Fibular neck
Mycoplasma and anemia
Cross rxn of IgM antibodies to red blood cells, activate complement and cause erythrocyte lysis
Cold agglutinins
Hemolytic anemia
IgM titers fall with infection resolution
Brain natriuretic peptide levels secreted from
Ventricular myocytes
Due to increased ventricular wall stress
5 y.o to ER iwth 2 days of dark, low-volume urine and decreased energy. Had abdominal pain, fever and bloody diarrhea after eatting hamburgers 3 days ago. No edmea or rashes. Anemia, thormocytopenia and elevated BUN and creatine.
See elevated waht
HUS from E.coli
Shigella toxin
Decease in hemoglobin and haptoglobin
Increase lactate dehydrogenase and unconjugated bilirubin levels
Bacteria virulence factor simlar to tropomyosin and myosin.
Fxn
M protein
Resist phagocytosis
Group A streptococcus
- S pyogenes
- cross rxn causes rheumatic carditis
What contributes to hypocalcemia in patient with chronic renal disease
Hyperphosphatemia
Phosphate binds free calcium and precipitates in soft tissue
Triggers fibroblast growth factor, which lowers phospahte levels by inhibiting 1 alpha hydroxylsae
Decreases production of 1,25 hydroxyvitamin D
Decreased pulmonary capillary wedge pressure
Right sided heart failure
Impaired blood flow from right ventricle to left side of heart
Drugs and renal failure
Acute interstital nephritis
Delayed puberty
Anosmia
Kallmann syndrome
Failure of GnRH secreting neurons to migrate from origin in olfactory placode to normal anatomic location in hypothalamus
Mutation KAL-1 gene
May have cleft lip or palate
Antibodies to phospholipase A2 (PLA2R)
Membranous nephropathy
Magnesium salts and aluminum hydroxide together for antiacid
Magnesium causes diarrhea
Aluminum hydroxide causes constipation
Both temporarily increase the gastric pH by neutralizing hydrochloric acid relieving reflux
Common source of hemorrhage from penetrating gastric ulcers
Right and left gastric arteries that run along lesser curvature of stomach
What if taking during pregnancy can cause oligohydramnios
ACE inhibitors and ARBs
Pleural effusion
- due to pressure changes
- due to inflammation
Pressure changes
- transudative
- heart failure
- cirrhosis
- nephrotic syndrome
Inflammation
- Exudative
- increase vascular membrane permeability
(infection, malignancy, rheumatic disease)
- fluid to serum ratio of protein > 0.5
3 week old
Abdominal distension
vomiting
blood streaked stools
Had normal stool and urine
X ray shows thin curvilinear areas of lucency that parallel the bowel of the lumen
Pneumatosis intestinalis (air in the bowel wall)
Necrotizing enterocolitis (NEC)
Man with behavioral changes
Lack of focus and poor memory
Involuntary jerky movements
Huntington’s disease
CAG trinucleotide repeats
GOF mutation
Abnormal protein build up causes loss of inhibitory (GABA) neurons
Atrophy of caudate nucleus
Hiatal hernia caued by
Circumferential laxity of the phrenoesophageal membrane
IgA dn C3 deposition in vascular lesions of thigh
Henoch-Schonlein purpura (HSP)
Saddle nose and oliguria
CXR?
Granulomatosis with polyangiitis (Wegeners)
Large nodular densities
Which testicular tumor is associated with each?
1) Composed of cytotrophoblasts and syncytiotrophoblasts?
2) May present initially with gynecomastia
3) Elevated AFP
4) Elevated beta-hCG
5) Histologic appearance similar to koilocytes (cytoplasmic clearing)
- Choriocarcinoma
- Leydig or sertoli cell tumor
- yolk sac tumor
- choricocarcinoma, embryonal carcinoma
- Seminoma
Which ovarian tumor matches each?
1) Estrogen secreting leading to precocious puberty
2) Produces AFP
3) Psammoma bodies
4) Testosterone secreting leading to virilization
5) Lined with fallopian tube like epithelium
6) Ovarian tumor + ascites + hydrothorax
7) Call-Exner bodies
8) Elevated beta-hCG
9) Resembles bladder epithelium
1) Granulosa theca cell tumor
2) Yolk-sac tumor
3) Serous cystadenocarcinoma
4) Sertoli-leydig cell tumor
5) Serous cystadenoma
6) Ovarian fibroma (meigs syn)
7) Granulosa cell tumors
8) Choriocarcinoma, dysgerminoma
9) Brenner tumor
Which embryologic structure of the heart gives rise to each of the following?
1) Ascending aorta and pulmonary trunk
2) Coronary sinus
3) Superior vena cava
1) Truncus arteriosus
2) Left horn of sinus venosus
3) Right common cardinal vein and right anterior cardinal vein
What is the antidote for
1) Iron
2) Lead
3) cyanide
4) Methomoglobin
5) Carbon monoxide
6) Methanol or ethylene glycol
1) Deferoxamine
2) EDTA , succimer, dimercaprol
3) Nitraites, hydroxycobalamin, thiosulfate
4) Methylene blue, vit C
5) 100% oxygen hyperbaric oxygen
6) Fomepizole, ethanol, hemodialysis
Wound healing after 1 week
Fibroblasts
Type III collagen replaced by type I collagen
Exudative vs transudate
- Looks like
- Lab
- Due to
Exudate
- Cellular (cloudy)
- Increased protein > 2.9 , increased LDH (vs serum)
- Lymphatic obstruction, inflammation, infection, malignancy
Transudate
- Hypopcellular (clear)
- Decrease protein < 2.5, decreased LDH vs serum
- Increased hydrostatic pressure (HF, Na retention)
- Decreased oncotic pressure (cirrhosis, nephrotic syndrome)
Hematogenous spread of carcinomas
Four Carcinomas Route Hematogenously
Follicular thyroid carcinoma
Choriocarcinoma
Renal cell carcinoma
Hepatocellular carcinoma
Low Vd
- compartment
- drug types
Intravascular
Large/ charged molecules
Plasma protein bound
High Vd
- compartment
- drug types
All tissues including fat
Small lipophilic molecules, especially if bound to tissue protein
Clearance (CL)=
Rate of elimination of drug/ plasma drug concentration
= Vd x Ke (elimination constant)
Ke= 0.7/t(1/2)
CL= (0.7 x Vd)/ t(1/2)
Half life (t1/2) =
- 7 x Vd/ CL
- 3 half lives = 90% steady state
% remaining 1 half life= 50% 2= 25% 3= 12.5% 4= 6.25%
Loading dose=
(Cp x Vd)/ F
F= bioavailability
IV F= 100%
Cp= target plasma conc at steady state
Maintenance dose=
(Cp x CL x tau)/ F
tau= dosage interval (time between doses, if not administered continuously, in hours)
Maintenance dose for 1 day= 24 hrs
Therapeutic index=
TD50/ ED50
Median toxic dose/ median effective dose
The higher the TI the safer the drug
Drugs with low Therapeutic index
Warning! These Drugs are Lethal
Warfarin
Theophylline
Digoxin
Lithium
Nicotinic ACh receptors are
Muscarinic ACh receptors are
Nicotinic ACh receptors are ligand gated Na/K channels
Muscarinic ACh receptors are G protein coupled receptors through second messengers
Alpha 1 fxn (3)
Increase vascular smooth muscle contraction
Increase pupillary dilator muscle contraction (mydriasis, dilation)
Increase intestinal and bladder sphincter muscle contraction
Alpha 2 fxn (5)
Decrease sympathetic (adrenergic) outflow Decrease insulin release Decrease lipolysis Increase platelet aggregation Decrease aqueous humor production
Beta 1 fxn (4)
Increase HR
Increase contractility (one heart)
Increase renin release
Increase lipolysis
Beta 2 fxn ( 7)
Vasodilation Bronchodilation (two lungs) Increase lipolysis Increase insulin release Decrease uterine tone ** Ciliary muscle relaxation Increase aqueous humor production
M1 fxn
M2 fxn
M3 Fxn
M1: mediates higher cognitive functions, stimulates enteric nervous system
M2: Decrease HR and contractility of atria
M3: Increase exocrine gland secretions, increase gut peristalsis, increase bladder contraction, bronchoconstriction, increase pupillary sphincter muscle contraction (miosis)
Conotruncal abnormalities associated with failure of
Neural crest cells to migrate:
Transposition of great vessels
Tetralogy of fallot
Persistent truncus arteriosus
Baby takes first breathe
Decrease resistance in pulmonary vasculature
Increase pressure in left atrium
Preload
- is what
- approximated by
- also measures
- decreased by
Pressure at end of diastole (relaxation) when ventricles are the fullest right before contraction.
Approximated by ventricular End-diastolic volume
Ventricles fill from atria, atrial pressure= preload
Decreased by venous vasodilators
Afterload
- approximated by
- decreased by
Approximated by Mean arterial pressure
Total peripheral resistance (TPR)
Decreased by arterial vasodilators
EDV =
Right atrial pressure
S1 heart sound
S2 heart sound
S1= mitral and tricuspid closing
S2= aortic and pulmonary closing
Beside maneuver
1) Inspiration
2) Hand grip
3) Valsalva, standing up
4) Squatting
1) Inspiration
- increases venous return to right atrium
- Increase Intensity of right heart sounds
2) Hand grip
- Increase after load
- Increase intensity of MR, AR, and VSD
- Decrease AS murmur
3) Valsalva, standing up
- Decrease preload
- Decrease intensity of most murmurs
- Increase intensity of hypertropic cardiomyopathy
4) Squatting
- Increase venous return, increase preload, increase afterload
- Increase intensity of AS, MR, VSD
Holosystolic murmur
Tricuspid regurg
Mitral regurg
Slurred curved upstroke (delta wave) between P and R
Wolff parkinson white
Abnormal fast accessory conduction pathway from atria to ventricle (bundle of kent) bypassing AV node
May result in SVT
Origination site of atrial fibrillation
Pulmonary vein ostia
Atrial flutter caused by
Large reentrant circuit that transverses the cavotricuspid isthmus (region of R atrial tissue between IVC and tricuspid valve annulus)
Atrial natriuretic peptide released due to
Increase in blood volume and atrial pressure
acts as cGMP
Vasodilation and Decreased Na reabsorption
Pulmonary capillary wedge pressure approximation of
left atrial pressure
Rheumatic fever
- valve
- tx
Early: mitral regurg
Late: mitral stenosis
Penicillin
Innumerable renal microaneurysms and spasms on arteriogram
Fever, WL, Headache
Abdominal pain
HTN
Polyarteritis nodosa
Drugs that cause pulmonary fibrosis
Amiodarone
Bleomycin
Busulfan
Drugs taht cause flushing
Vancomycin
Niacin
Adenosine
Dihydropyridine Ca channel blockers
Drugs that cause Torsades de pointes
Potassium channel blockers Na channel blockers Macrolides Haloperidol Chloroquine Protease inhibitors
Drugs that cause gingival hyperplasia
Phenytoin
Verapamil
GI bleeding
Buccal pigmentation
Peutz jegher syndrome
Tuberous Sclerosis
HAMARTOMASS
Hamartomas in CNS and skin Angiofibromas Mitral regurg Ash lead spots Cardiac rhabdomyoma Tuberous sclerosis autosomal dOminant Mental retardation renal Angiomyolipoma Seizures Shagreen patches
78 y.o to office with one month history of progressive dyspnea, generalized weakness, fatigue and palpitations. He reports tingling and numbness in both lower limbs. Hes not been taking care of himself since wife died. CV exam shows displaced apical impulse at 6th intercostal space, a third heart sound, and high volume carotid pulses. Pedal edema, mild hepatomegaly. Normal blood counts. What deficiency?
A. Ascorbic acid B. Cobalamin C. Niacin D. Pyridoxine E. Retinol F. Riboflavin G. Thiamine
G. Thiamine
Wet beriberi
- peripheral neuropathy
- heart failure
Person dies after 5 days from heart failure due to
Free wall rupture –> Profound hypotension and shock
History of mitral valve prolapse. Temp of 100. Mid systolic click systolic murmur at apex. Gram positive bacteria that synthesizes dextrans from glucose. Adherence of bacteria would be where?
A. Circulating heparins B. Endothelial surface glycoproteins C. Fibrin platelet aggregates D. Subendothelial collagen E. Subendothelial glycosaminoglycans
C. Fibrin platelet aggregates
Virdians streptococci. Produce dextrans which facilitate adherence to fibrin.
Fibrin and platelets are deposited at sites of endothelial truma
What is similar in parameters between systemic and pulmonary circulation
A. Arterial oxygen content B. Arterial resistance C. Blood flow per minutes D. Diastolic arterial pressure E. Driving pressure for blood flow F. Mean arterial pressure
C. Blood flow per minute
Superior gluteal and inferior gluteal come off
Internal iliac
also obturator comes off
Chronic anemia on cardiac output and venous return curves
Increase in cardiac output
Somewhat increase in venous return
Anaplylaxis effect on cardiac otuput and venous return curves
Widespread venous and arteriolar dilation
Drop in venous return (shifted down and leftward)
1 week old infant
Discharged at 30 hrs
PE harsh, holosystolic murmur at left mid to lower sternal border
No murmur heard at birth
Non-cyanotic possibilities
- Atrial septal defect
- VSD
- PDA
- Coarctation of aorta
Patients presents w/ VSD
- loud blowing holosystolic murmur
What chemical substance help decrease thrombus propagation by inhibiting platelet aggregation?
Prostacyclin
Normal cardiac pressures
1) RA
2) RV
3) Pulmonary artery
4) Pulmonary artery wedge
5) LA
6) LV
7) Aortia
1) RA= < 5
2) RV= 25/5
3) Pulmonary artery= 25/10
4) Pulmonary artery wedge= < 12 (10)
5) LA= < 12 (10)
6) LV= 130/10
7) Aorta= 130/90
Atrial myxoma on histology
Amorphous extracellular matrix
With scattered stellate or globular myxomas cells within abundant mucopolysaccharide (myxoid) ground substance containing chondroitin sulfate and hyaluronic acid
Common cardinal veins form
Superior vena cava
Disorder in which no finding can be found to support symptoms but recently had trauma or stress in life
Conversion disorder
Cachectin caused by
TNF-alpha
IL-1
IL-6
Liver mass that is a cystic lesion
Hepatomegaly
- microscopic examination
- complication of treatment
Echinococcus granulosus
Hydatid cysts
Sheep/ dog expsoure
Eggshell calcifications
Caution with removal –> spilling of cyst contents can cause anaphylactic shock
Blistering in sun
Itchy
Porphyria cutaneous tardia
Uroporphyringoen decarboxylase
Painful genital lesion, irregular ragged borders
Grey excudatecovering
Enlarged inguinal LN
Chancroid`
Fatigue
Early satiety
Mucosal pallor with no scleral icterus. Lungs clear. Mild hepatomegaly. Can feel tip of spleen. Pancytopenia. Peripheral blood= immature granulocytes, nucleated erythrocytes and teardrop cells. BM aspiration is attempted but yields no marrow
- disease
- MOA
- Secretes
- Symptoms
- Histopathylogical features
Primary myelofibrosis
Chronic myeloproliferative disorder with clonal megakaryocytes
Secrete TGF-beta –> fibroblasts to produce collagen and BM fibrosis
–> Extramedullary hematopoiesis
Massive splenomegaly
Tear drop cells
Dry tap
Large islands of hematopoietic progenitor cells
Spleen histopathyology
1) Accumulation of macrophages with fibrillary cytoplasm
2) Diffuse neutrophilic infiltration and follicular necrosis
3) Dilated sinusoids and fibrosis nodules with hemosiderin
1) Gaucher disease
- AR lysosomal storage disease
- fibrils of glucocerebroside
(Crumped tissue paper)
2) Acute infection of spleen
Follicular necrosis= infection group A strep
3) Congestive splenomegaly due to portal HTN
Dermatomyositis
- biopsy shows
- can affect
Proximal muscle weakness
Rash on eyelids
Affects striated muscles and skin
Oropharynx and upper esophagus
Perimysial inflammatory infiltrates and atrophy involving the fibers around the periphery of muscle fascicles (perifascicular atrophy)
Eosinophilic esophagitis presents as
Dysphagia
Epigastric pain
Recurrent esophageal relfux
Food impaction
NE leak into arm causes
Tx
Alpha 1 receptor mediated vasoconstriction which can lead to tissue necrosis
Tx Phentolamine (alpha receptor blocker)
Thyroid Fine needle aspiration biopsy
Clusters of cells with large overlapping nuclei containing sparse, finely dispersed chromatin
Numerous intranuclear inclusion bodies and grooves are seen
Papillary carcinoma
Overlapping nuclei containing finely dispersed chromatic (empty or ground glass appearance= orphan annie eyes)
Unusually muscle movements of thumb Hypoplastic mandible Low set ears Bifid uvula Cleft palate
Physical features of DiGeorge syndrome
Hypocalcemia
Heme synthesis occurs where
Mitochondria
New born with drug addict mother. Irritable, crying, tremors, sneezing and diarrhea
Tx
Opioid withdrawal
- Neonatal abstinence syndrome
Morphine
Methadone
COPD lung volumes
Air trapping and hyperinflation
Higher functional residual capacity
Higher reserve volume
Total lung capacity increases as well but to a lesser extent
High RV/ TLC ratio
Diffusing capacity of lung for carbon monoxide is decreased
- due to emphysematous destruction of the alveolar arterial membrane
FEV1 decreased
FVC decreased
FEV1/FVC decreased
Loss of internal elastic lamina
Fibromuscular dysplasia
Luminal stenosis alternating with areas of dilation
Resistant HTN
Stroke
Ruptured aneurysm
Renal artery stenosis
Cerebrovascular involvment
Other form of downs syndrome
Trisomy 21
46, XX t(14;21)
Robertsonian translocatoin
HTN
Suppressed Renin
Na?
K?
Bicarb
Primary aldosteronism
High Na
Low K
Low Bicarb
Sudden cardiac death due to
Ventricular fibrillation
- Lack of tissue perfusion due to blockage
Horseshoe kidney associated iwth
Turner
Schistocytes associated with
HUS, TTP, DIC and AORTIC STENOSIS
Structure gives rise to heart structure
1) Smooth parts of left and right ventricles
2) Smooth part of right atrium
3) Trabeculated left and right atria
4) Trabeculated parts of the left and right ventricles
1) Smooth parts of left and right ventricles
- Bulbus cordis
2) Smooth part of right atrium
- Right horn of sinus venosus
3) Trabeculated left and right atria
- Primitive atria
4) Trabeculated parts of the left and right ventricles
- Primitive ventricle