More enzymes to know

PKU  = lack of Phenylalanine hydroxylase or its cofactor tetrahydrobiopterin (substantia nigra can show pallor, don't be fooled it is not Parkinson's, PKU patients are toddler's) 

Biosynthesis of norepinephrine from dopamine = dopamine hydroxylase 

Most common Arrhythmia = Atrial fibrillation

ECG characteristics:

Absent P waves replaced by fibrillatory (f) waves

Irregular R-R intervals

Narrow QRS compexes

Normal heart = an electrical pulse is generated in the SA node, transmitted to the right atrium, the to the left atrium via interatrial pathway. 

In atrial fibrillation the ventricular rate is lowered to 90 - 170 beats/minute from normally 300-500 beats/minute. The AV node is the bottle neck in atrial fibrillation. AV node refractory period determines the ventricular contraction rate.

Atrial Fibrillation = occurs due to irregular chaotic electrical activity in the atria. Some atrial impulse make it to the ventricles but most do not due to the AV refractory period

Lecithin-sphingomyelin ratio

a ration of 1.9 is considered to indicate fetal lung maturity. 

The cortisol from the fetus and mother play a stimulatory role in the development of the lungs which will show a higher Lecithin to Sphingomyelin ratio.

Unrelated:

but do not for get that the enzyme deficiency in Niemann-Pick is sphingomyelinase so there is a build up of sphingomyelin

Vertical Diplopia

Double vision when looking the affected eye is looking down and in like when reading a newspaper or going down stairs.

This is caused from a lesion to cranial nerve IV (Trochlear)

Lesions to cranial nerve VI (abducens) can cause horizontal diplopia and estropia (inward deviation). Muscles affected = lateral rectus

Lesions to CN III (occulomotor) can cause vertical and horizontal diplopia, ptosis, enlarged and non-reactive pupil. Muscles = superior rectus, medial rectus, inferior rectus and inferior oblique

Hypothalmic-pituitary-adrenal (HPA) axis suppression

This is the most common cause of adrenal insufficiency 

Long-term use of gluccocorticoids can cause this, and it is characterized by:

low CRH

low ACTH

low cortisol

The patient will have a low BP due to the low cortisol

In a healthy individual CRH stimulates ACTH which in turn stimulates Cortisol.

Normally Cortisol provides negative feedback for CRH and ACTH so when a patient has ectopic secretion of cortisol you will see decreased CRH and ACTH

Psych bable

Transference = Patient says: "stop treating me like a baby, you remind me of my mother who treated me like a baby" 

Projection: Patient accuse the doctor of sexual interest in him, when actually the patient likes the doctor.

Displacement = A resident is yelled at and so later he yells at a medical student.

Down's Syndrome and cancer

Increased risk of AML-M7 (500 fold)

Increased risk of ALL (10 fold)

Other info

95% = meitotic non-disjunction 

4% = robertsonian translocation

Inherited disorders caused by deficient DNA-repair enzymes

Ataxia-telangiectasia = DNA hypersensitivity to ionizing radiation = cerebellar atrophy, repeated infections, increased malignancy

Xeroderma pigmentosum = DNA = hypersensitive to UV radiation due to failed nucleotide excision repair. Increased for all types of skin cancer: basal, squamous, melanoma

Fanconi anemia = DNA can't repair damage from cross-linking agent exposure

Bloom Syndrome = generalized chromosoma instability. Increased risk of neoplasma.

Hereditary Nonpolyposis colorectal cancer (HNPCC), defect in DNA mismatch repair = leads to colon cancer

Leukocyte esterase test, Nitrite test

Leukocyte esterase + = presence of neutrophils (Bacterial infection)

Nitrite + = Gram- negative Most enterobacteria (gram-negative enteric rods) are able to form nitrite from nitrate

Easy enough! It gets trick when the patient is Leukocyte esterase positive and Nitrite negative.

So you know it is going to be Gram positive bacteria causing the infection. Most likely would be Staph. saprophyticus (2nd most common cause of UTI in sexually active females). The other possibility which is not as common is Enterococcus faecalis (gram positive, catalase-negative)

Nodular

We all know that exposure to vinyl chloride found in the rubber industry increases one's risk for liver cancer. 

What is the cancer and what does it look like?

Angiosarcoma = gross and microscopic features - multinodular

Highly aggressive, arrises from blood vessels

Achalasia

Achalasia:

Inability of the lower esophageal sphincter to relax during swallowing. 

Often the boards throws this symptom out as a distractor for a patient with GERD, which can be due to the lower esophageal sphincter relaxing at the wrong time (when not swallowing) this allow acid to reflux into the esophagus.

Caused by lack of Vasoactive Inhibitory Peptide (VIP), loss of myenteric (Auerbach's) plexus in the muscularis externa.

Abnormal contractions along the entire esophagus affecting lower, middle and upper esophagus. 

Key Symptom to differentiate from Odynophagia =

In Achalasia patients will have dysphagia to solids, liquids or both with or without pain Odynophagia = painful swallowing of food (usually). Odynophagia is the main symptom of esophagitis and esophogeal candidiasis

Swallowing reflex is initiated by the somatic nervous system (voluntary) and then becomes autonomic (involuntary).

There will be increased pressure lower esophageal sphincter (LES)

Poor peristalsis 

Barium swallow = initial test = "Bird's Beak" sign = distended esophagus with narrowing at the LES = hallmark for Achalasia

Best Dx test = manometry of esophagus will show aperistalsis, increases LES pressure, incomplete sphincter relaxation with swallowing.

Don't be fooled:

Dysphagia = difficulty with swallowing seen in achalasia 

Odynophagia = pain with swallowing = esophagitis and esophageal candidiasis.

Esophogeal Cancer = patients present with difficulty swallowing, 1st to solids then later to fluids.

Zenker Diverticulum = pouch in esophagus associated with halitosis and feeling of food being stuck in esophagus.

Esophogeal Web (Plummer Vinson syndrome) = associated with iron deficiency anemia, difficulty swallowing solids

Charcot's Triad Squared

Yes there are 2 different Charcot's Triads both for different diseases.

Charcot's triad 1: used for detecting MS

Nystagmus 

Intention Tremor

Scanning speech

Charcot's Triad 2: used for detecting ascending Cholangitis

Jaundice

Fever (usually has rigors as well)

Right Upper Quadrant (RUQ) pain

If the Charcot's Triad 2 presents with hypotension then it changes to Reynold's Pentad

Bence-Jones

Bence-Jones protein:

Multiple Myeloma, caused by urinary excretion of myeloma light chains (K or L)

Waldenstrom's macroglobulinemia (IgM)

Schilling Test

You have a patient who has Macrocytic Anemia and you have done neuro exam and have determined there are neuro problems so now you know that your patient has a Vitamin B12 deficiency not a folate deficiency. 

How do you determine what is causing the Vitamin B-12 deficiency?

The answer is the Schilling test but let's break it down further. The point of the Schilling test is to determine if the B-12 deficiency is from Lack of dietary intake or Pernicious Anemia, or Malabsorption

Step 1 = Inject the patient with pure B-12 and this will saturate all the B-12 storage places (liver). now have the patient drink radio labeled B-12 and when the radio-labeled B-12 gets to the liver and tries to get stored it is turned away as there is no room left because of the pure B-12 previously injected. When it is turned away it goes to the kidney and gets pissed out. 

 

Normal = 5%: 

If the patient's urine has 5% radio-labeled B-12 in it then it is normal and you have ruled out malabsorption issues including pernicious anemia (lack of intrinsic factor). Patient is Normal. So the B-12 deficiency could be to plain lack of dietary intake. Tx = vitamin b- 12 supplements.

Deficient = less than 5%:

If the patients urine contains less than 5% radio-labeled B-12 then you know that the patients B-12 deficiency is caused by pernicious anemia (loss of Intrinsic factor) or other malabsorption problems

Step 2: Now to distinguish between pernicious anemia and other malabsorption pathology:

Inject pure B-12 with Intrinsic Factor. Then have the patient drink radio labeled B-12. 

If the patient's urine contains 5% radio-labeled B-12 you will know that the Vitamin B-12 deficiency is due to lack of Intrinsic Factor (Pernicious Anemia). 

If the patient's urine has less 5% radio-labeled B-12 then you have ruled out pernicious anemia, which means that the B-12 deficiency is due to other malabsorption issues which has numerous causes. 

Step 3: To rule out Chronic Pancreatitis as a cause of malabsorption leading to B-12 deficiency, You can give the patient pancreatic enzymes and the follow it with radio-labeled B-12. If the 24 hour urine has 5% B-12 the you have Diagnosed B-12 deficiency due to chronic pancreatitis. Pancreatitis causes B-12 deficiency because there are pancreatic enzymes necessary to cleave the R-factor off of the B-12 - R-factor complex. If these enzymes are absent then the body can't absorb the B-12. If there is less than 5% B-12 in the urine then you have ruled out Chronic Pancreatitis. 

Step 4: Now you can rule out Bacterial overgrowth by giving the patient a 10 day coarse of broad spectrum antibiotics followed by radio-labeled B-12. Then if the patient's 24 hour urine has 5% (normal) B-12 in it then you have diagnoses Vit B-12 deficiency due to Bacterial Overgrowth. If there is less than 5% B-12 in the urine then you have ruled out bacterial overgrowth.

If you make it to this point with the patient and you still do not have you diagnosis you must assume the B-12 deficiency is due to something other than what you ruled out. There are many other causes but the Schilling Test rules out or rules in the more common causes. Some other causes could be:

Crohn's disease, Diphyllobothrium latum (fish tape worm), and others.

Microcytic

Microcytic Anemias.

Why are the RBC's smaller than normal? Well there is a decrease in the synthesis of hemoglobin and and this shortage acts as a signal to induce more cells division cycles as in mitosis. When a cell goes through mitosis it gets smaller. The more divisions the smaller it gets. So since all microcytic anemias have a decrease in hemoglobin synthesis the RBC's are signaled to divide and they become small, hence the term Microcytic.

There are 4 types of microcytic Anemia:

1.) Iron Deficiency Anemia 

2.) Anemia of Chronic Disease

3.) Thalassemia (Beta & Alpha)

4.) Sideroblastic Anemia (Alcohol, Vit B-6 deficiency, Lead poisoning) 

EKG

Ventricular Fibrillation:

Random electrical activity with no recognizable QRS complexes

Premature Ventricular Contraction:

Ectopic ventricular pacemaker inserts an ectopic beat = wide and bizarre QRS complex before the next sinus beat occurs

Ventricular Tachycardia:

Wide and bizarre but recognizable QRS complexes occur at an accelerated rate

Shoulder Movements

Rotator Cuff Muscles:

Subscapularis = Internal Rotation

Infraspinous = External Rotation

Supraspinatous = Abduction of arm at the shoulder

Teres Minor = External rotation

Sperm, Sperm everywhere

Spermatogenesis:

Spermatogonia (2N) to Primary Spermatocytes (4N) to Secondary Spermatocytes (2N) to Spermatids (1N) to Spermatozoa

Spermatogonia are found in basal lamina of seminiferous tubules. More mature forms are found more centrally.

Celiac Sprue

Celiac Sprue: (gi disease due to reaction to gliadin, found in gluten (wheat))

Associated with the following antibodies: anti-gliadin, anti-endomysial, reticulin antibodies

Increased risk of developing gastrointestinal lymphoma

Jejunal biopsy will reveal marked atrophy of villi.

Tx = gluten free diet!

Chylomicrons

Chylomicrons:

Lipoproteins that carry triglycerides and cholesterol from intestine to tissue.

Lipoprotein Lipase = enzyme required for the metabolism of chylomicrons and VLDL.

Lipoprotein Lipase is found in the endothelial cells lining the capillaries.

Southern Northern Western

Southern Blot = DNA (Down South, D for DNA)

Northern Blot = RNA

Western Blot = Protein 

Simple enough

11, 17 or 21 alpha-hydroxylase deficiencies

Let's keep this real short and sweet and hopefully easy to remember.

21 alpha-hydroxlase deficiency: (masculinization, pseudohermaphrodite) 

the most common congenital adrenal hyperplasia syndrome

Key feature = Hypotension and dehydration (salt wasting)

11 alpha-hydroxlase deficiency: (Masculinization)

Key feature used to distinguish 11 from 21 = hypertension due to increased mineralcorticoids

17 alpha-hydroxylase deficiency: (fails to mature sexually)

phenotypical female but never matures = no sex hormones = this distinguishes it from 11 because 17 has increased mineralcorticoids and hypertension as well. 

Alpha-fetoprotein

What is this stuff?

 Alpha-fetoprotein is the albumin of the fetus

What do we need to know about it?

It is a tumor marker for some tumors:

Yolk sac tumors (endodermal Sinus tumors) 

Tumors in the ovaries of young girls or testes of young boys are most often Yolk Sac

Hepatocellular Carcinoma

Marker for fetus issues:

If the fetus has an open neural tube defect alpha-fetoprotein will be elevated

If the fetus has down's syndrome (think down) alpha-fetoprotein will be low

We all know that folate taken prior to conception is protective against neural tube defects. 

Tinnitus, bear hunting, gin and tonic

Tinnitus = Ringing in the ears

2 main drugs have this side effect.

First = Aspirin = tinnitus is often the first sign of an overdose.

Second = Quinidine = Class A1 anti-arrythmic. This drug has quinine in it which is also found in tonic water. Quinine can be used for treating arrythmias but it can also be used for drug resistant malaria, nocturnal muscle cramps, or as an abortifacient. The tinnitus it causes is part of a group of side effects from quinine called Cinchonism.

What in the hell is Cinchonism? You know that they will not use that term on the boards but instead they will describe it and we will have to know what drug caused it or something like that. So knowing that Quinidine can cause Cinchonism does not do Jack if you can't identify the symptoms. Here they are: Ringing Ears, abdominal pain, headaches, flushing, rash, confusion, reversible hearing loss, dizzy, etc. 

Here is the Question: A man who returned from a safari in africa 6 months ago shows up at your ER feeling awful (dizzy, rash etc) and complaining of ringing is his ears. He mentions that he "caught something" while on his trip and that his primary care doctor has been trying to treat it but recently had to switch up the medications because they were not working. When you ask him what he "caught" he misunderstands you and begins to show you pictures of his hunting kills from the safari but fails to remember the disease. When you see a picture of him with a dead bear he killed, you remind him not to eat Bear liver because it has too much Vitamin A and could cause Vitamin A toxicity leading to cerebral edema and even death. He responds by saying he is going to stop eating anything with Vitamin A in it at all and you explain to him that is a bad idea because Vitamin A deficiency is associated with Nyctalopia (night blindness) and you explain that Vitamin A helps prevent metaplasia. With a confused look on his face he asks you why his ears are ringing. What common drink served in bars would you tell this patient to avoid?

A.) Schlitz 

B.) Root Beer

C.) Bloody Mary

D.) Gin and Tonic

E.) Mad Dog 50/50 

Answer = Gin and Tonic. The patient is being treated for resistant malaria with a drug that contains quinine. A side effect which his symptoms match = cinchonism is caused by quinine also found in Quinidine (class A1 anti-arrythmic). So drinking tonic water would only add to the problem. The bear liver and Vitamin A was just extra fun stuff but true!

Ectopic Forensics

Patient presents with: Hyponatremia or Cushings, What cancer do you think of?

Small Cell Carcinoma (S100 marker, neural crest origin) 

Ectopic ADH causes Hyponatremia

ACTH causes Cushings

Hypocalcemia or Secondary Polycythemia?

Renal Adenocarcinoma

PTH-like peptide causes hypercalcemia 

Erythropoietin causes secondary polycythemia 

Hypoglycemia or Secondary Polycythemia?

Hepatocellular Carcinoma

Insulin-like factor = Hypoglycemia

Erythropoietin = Secondary Polycythemia

Hypocalcemia?

Medullary Carcinoma of the Thyroid

Calcitonin = tumor marker get turned into amyloid so it can no longer stimulate osteoclasts to break bone down = hypocalcemia

Shout out to Goljin 

Pharm Giveme's

Malignant hyperthermia:

Halothane + succinylcholine

Tx with Dantrolene 

Local Anesthetics 

Esters only have 1 "i" in there name 

Amides have 2 "i's" in their name plus Amide has an "i" in its name to remind you 

Esters:

Cocaine

Benzocaine

Procaine

Tetracaine

Amides:

Lidocaine

Mepivacaine

Bupivacaine

Prilocaine

More to come later.

What is wrong with your head?

Depigmentation of the substantia nigra and locus ceruleus = Parkinson's

Lewy bodies

Diffuse cortical atrophy with relative sparing of primary motor and sensory areas = Alzheimer's

Beta Amyloid plaques, neurofibullary tangles

Selective frontal and temporal lobe atrophy, gliosis, neuronal loss, swollen neurons = Pick Disease

Pick Bodies (silver staining cytoplasmic inclusions)

Striking degeneration of the caudate nucleus = Huntington's (autosomal Dominant)

Widespread neuronal loss and gliosis in subcortical areas = Supranuclear Palsy

Rabies = Negri bodies

Turner

When someone says Turner Syndrome, what do you think about?

Aortic Coarctation (preductal type):

hypotension and lower extremity cyanosis which causes rib notching = erosion of lower border of the ribs from enlargement of the intercostals which provide collateral blood flow

Primary Amenorrhea 

Ovary streaks = lack of sex hormones 

Most common sex chromosome abnormality in females

Complete or partial monosomy of the X chromosome (45XO)

50%+ = complete loss of the X chromosome = no Barr body the remaining = mosaicism (46XY) which makes the at risk for gonadoblastoma

Patient described as Short, wide spaced nipples, delayed puberty, weak pulses of lower extremities, can have hypothyroidism and diabetes. Xray - rib notching.

That is what I think of when I here Turner Syndrome. 

Turner = trapped in Tanner stage 1

Cancer Chemo and Allopurinol

A patient who is going to have chemotherapy and there is going to be a high cell turnover rate like in leukemia and lymphoma Allopurinol should be given as a prophylaxis for uric acid stones.

Allopurinol = prodrug converted by xanthine oxidase, forming alloxanthine which inhibits xanthine oxidase (suicide substrate). 

Inhibiting xanthine oxidase = decreases purine metabolism, which decreases uric acid which decreases uric acid stones. 

Allopurinol is used in gout.

It also inhibits the metabolism of 6-mercaptopurine raising its toxicity. 

Side effects = GI, peripheral neuropathy, rash, vasculitis and stone formation.

I-cell Disease

What is I-cell disease?

Autosomal Recessive lysosomal storage disorder.

Abnormalities give rise to connective tissue that is called inclusion bodies which is where the disease gets its name I = inclusion bodies.

Normally the cell will tag (mark) lysosomal enzymes with mannose-6-phosphate to direct them to the lysosomes. It is like the cell gives the enzyme a map to the find the lysosomes. In I-cell disease there is a defect in the addition of mannose-6-phosphate. This causes the lysosomal enzymes to get lost and they get released into the extracellular space and because they never find the lysosomes the lysosomes are empty and lack the important enzymes they need to break things down. 

Features of I-cell disease:

Coarse facial features like thick gums (gingiva hyperplasia like a side effect of phenytoin) and a large tongue (glossitis) 

Skeletal abnormalities like congenital dislocation of the hip or clubbing of the feet Psychomotor retardation or immobility of extremities. Failure to thrive.

The boards can test this concept in a couple of ways:

They can ask where does the lysosomal enzymes get released in I-cell disease. 

Answer = ECM

They can also ask about the defect of I-cell disease. 

Answer = phosphorylation of mannose = defect in the addition of mannose-6- phosphate moiety to the lysosomal enzymes. 

Finally they can ask about features of the lysosomes in I-cell disease. 

Answer = they are empty = defective.

In every question they will give hints by describing the features of the patient with the above abnormalities, often the patient is an infant as I-cell presents at birth

Finally = the absolute details:

Deficient enzyme = UDP-N-acetylglucosamine-1-phosphotransferase due to a mutation of the GNPTA gene.

The accumulation = the misguided lysosomal enzymes

I-cell is said to be similar to Hurler syndrome but more severe.

So we have Hunter's syndrome (X-linked , Hunters aim for the X) which is a like milder form of Hurlers's and now I-cell disease which = more severe than Hurler's.

Hunters:

Deficient enzyme = Iduronate Sulfatase. Accumulates Heparan Sulfate and dermatan sulfate. Features = Milde Hurler's plus aggressive behavior and no corneal clouding

Hurler's 

Deficient enzyme = alpha-L-iduronidase. Accumulation is Heparan Sulfate and Dermatan Sulfate. Features = Developmental Delay, gargoylism, corneal clouding.

Last but not least, when I think of I-cell disease I also remember Chediak-Higashi because this disease has some common themes with I-cell:

Chediak-Higashi:

Autosomal Recessive

Microtubule defect which messes up lysosomal emptying of phagocytic enzymes.

Presents:

Recurrent pyogenic infections by Staph and Strep, partial albinism, and peripheral neuropathy.

I-cell has empty lysosomes because the enzymes were misguided and got released into the ECM rather than being put in the lysosomes,  so the Lysosomes do not work properly. Chediak-Higashi = lysosomes have defective emptying so the lysosomes do not work properly. Both = autosomal recessive.

Osteoblastic or Osteolytic

Ok you need to know which cancers are Osteolytic and which are osteoblastic.

Osteolytic = breaks bone down so osteoclasts are involved and enzymes like IL-1 and PGE2 are involved and stimulate the osteoclasts. Patient often has hypecalcemia. 

Osteoblastic = builds bone so like the name suggests, osteoblasts are involved. The Alkaline Phosphatase would be elevated.

Lung = lytic

Prostate = Blastic

Breast = Both lytic and blastic

Multiple Myeloma = Lytic (cookie cutter lesions) 

Dopamine, Dopamine, Dopamine

D1, D2, D3, D4, D5

So lets say runners D1, D2, D3, D4, D5 are all in a marathon. The 1st and last place are the most excitatory positions. Everyone wants to be in first place (D1) so they are motivated (excitatory) to run faster. No one wants to be in last place (D5), so they are motivated (excitatory) to run faster so they are not last. This will help you remember that: D1 & D5 are excitatory and the rest (D2, D3, D4) are inhibitory.

Excitatory:

D1 & D5

Stimulate kidney during shock

Inhibitory:

D2, D3 & D4 The schizophrenic drugs act on D2 which inhibits dopamine

Dopamine works on G protein cAMP 2nd messengers 

Back to the runner analogy. Imagine that many runners are also love the outdoors so they also like to camp. This should remind you that cAMP is the 2nd messenger of dopamine.

Interferons

IFN-alpha = Hep B and C and Kaposi's sarcoma

IFN-beta = MS

IFN-gama = NADPH oxidase deficiency (Chronic Granulomatous Disease)

IFN-gama 

Made by T-cells = CD4+ T-cells = Th1 cells. IFN-gama activates macrophages but it also inhibits, the Th2 cells 

AIDS therapy

I am going to breakdown AIDS treatment on a basic level. Someone has AIDS, what can you do?

Here are the options:

Protease Inhibitors

Reverse Transcriptase Inhibitors

Nucleosides 

non-nucleosides

Fusion Inhibitors

Protease Inhibitors:

All the Navirs

Saquinavir

Ritonavir

Indinavir

etc

MOA:

These drugs block the protease in progeny virions, thus inhibiting assembly of new virus

Reverse Transcriptase Inhibitors:

Nucleosides:

Zidovudine (ZDV) used to be called AZT

Didanosine(ddI)

Zalcitabine (ddC)

Stavudine (d4T)

Lamivudine (3TC)

Abacavir

Non-nucleosides:

Nevirapine

Efavirenz

Delavirdine

MOA:

These drugs block the transcriptase of HIV thus preventing the incorporation of DNA copy of viral genome into host DNA

Fusion Inhibitors:

Enfuvirtide

MOA:

Bind the viral gp41 subunit and block the conformational change required for fusion with CD4 cells = block entry of the virus

Now AIDS treatment is way more complicated than noted here and most patients are on several medications. This is just a basic snap shot of some of the current therapies. 

Protease Inhibitors, Reverse Transcriptase Inhibitors and Fusion Inhibitors

Shout out to First Aid!!

Women, Menopause and Osteoporosis

We all know that women are at a very high risk of osteoporosis after menopause, but the question is why? Well the easy answer is no estrogen. This will not cut it for the boards. So you may know all of this already but it can't hurt to review it and let me know if I made a mistake.

Osteoporosis = The body breaks more bone down than it builds. 

So we have osteoblasts which build bone. We have osteoclasts which break bone down for the calcium and put the calcium into the blood. We have 2 important receptors on our Osteoblasts (I am sure there are many more than 2). One receptor = is for Vitamin D. Vitamin D hooks into the receptor and causes the enzyme Alkaline Phosphatase to be released. So whenever we are building or making bone we should have an elevated alkaline phosphatase level. 

The other receptor on the osteoblasts is a receptor for PTH. Now when PTH hooks into its receptor on the osteoblasts it releases IL-1 (also known for fevers, stimulating antibody synthesis, B-cell stimulation etc) in this case IL-1 is called osteoclast activating factor. IL-1 goes over to the osteoclasts and stimulates them to start breaking bone down, which they do and this raises are blood calcium levels. So when we need calcium, this is a good thing. Normally IL-1 is kept in check by our sex hormones, like testosterone in men and estrogen in women. The estrogen blocks the IL-1 from going too crazy. 

After menopause when women do not have any more estrogen or in athletes or anorexics who have low levels of estrogen there is nothing to inhibit IL-1 and it over stimulates the osteoclasts and they breakdown too much bone and you get a pathologic fracture of the hip, get hospitalized and get nosocomial pneumonia and die!

That is why postmenopausal women get osteoporosis. 

Shout out to Goljan!

Embryo Ectoderm

How high yield is Embryo??? Well I think most of it can be quickly memorized right before the exam but here are some of the key structures and where they originated from:

You must know the 3 basic types of origination:

Ectoderm, Mesoderm and Endoderm

Here is some ectoderm to think about!

In Ectoderm you have sub classes Surface Ectoderm, Neuroectoderm and Neural Crest

Surface Ectoderm:

Epidermis

Hair

Nails

Inner Ear, External Ear 

Enamel of teeth

Lens of eye

Anterior Pituitary (Rathke Pouch)

Parotid Gland

Neuroectoderm:

Neural tube

CNS

Retina and optic nerve

Pineal Gland

Neurohypophysis

Astrocytes 

Oligodendrocytes

Neural Crest:

Adrenal Medulla

Ganglia:

Sensory and Autonomic

Pigment Cells

Schwann Cells

Meninges

Pia and arachnoid mater

Pharyngeal Arch Cartilage

Odontoblasts

Parafollicular (C) cells

Aorticopulmonary Septum

Endocardial Cushions

They like to trick you up on the neural crest cells. SO they may ask you about a sick infant and give all the symptoms of Hirschprungs / megacolon and than ask you something like. "the cells involved in this disease come from the same origin of which of the following?" then they list a bunch of garbage. In the mean time your still trying to figure out what is wrong with the kid! Well he is missing cells that run his enteric nervous system of his gut. Those cells have a neural crest origin like all ganglia. So in the answer choices you want to find something that also originates from neural crest cells, like dental pulp = odontoblasts.

Potter

Don't you hate it when you think you understand a concept very well and then you come across some random question involving the concept and you think "no problem" I know this concept, but as you read the question you realize that the question is asking about some aspect of the concept than you do not understand! This occurred to me with Potter's syndrome. I am going to try and cover every aspect that could be tested regarding Potter Syndrome. Well not every aspect.

Potter Syndrome = results in oligohyraminos = low amniotic fluid this is secondary to renal disease, most commonly renal agenesis. So the baby can't pee which normally adds to the amniotic fluid. The baby gets deformed because the is no fluid to provide cushioning. The deformities are caused by pressure from the baby being smashed. Deformities = flattened facial features, low set ears, deformities of the feet.

This all seems pretty straight forward right. Well you have to remember that the kidneys can fail to develop if the urteric buds fail to develop. Ureteric buds form ureters, renal pelvis, calyces and collecting tubules. The collecting tubules induce formation of metanephric vesicles which differentiate into tubular components of the nephron.

They can ask which of the following malformed structures can lead to Potter's? look for the answer with Ureteric Buds!

Also kidneys or metanephros (adult kidney) form from what type of cells? Answer = mesenchymal stem cells, mesoderm. They got me with this one once too.

Also these babies fail to develop lungs and shortly after birth they can go into respiratory distress from Pulmonary Hypoplasia

That is all I can think of right now but I am sure there are more ways that they can take a concept that you mastered and screw you up!!

Acid Base

Who hates this stuff? Answer = me.

pH = [HCO3-]/pCO2

Anything that increases bicarb (HCO3-), increases pH = alkalosis (metabolic)

Anything that decreases pCO2, increases pH = alkalosis (respiratory)

Anything that decreases bicarb (HCO3-), decreases pH = acidosis (metabolic)

Anything that increases pCO2, decreases pH = acidosis (respiratory)

Anything that decreases H+, increases pH = alkalosis (respiratory)

Anything that increases H+ decreases pH = acidosis (respiratory)

Hyperventilation = breathing out CO2 thus decreasing pCO2 which causes increase in pH = respiratory alkalosis Which is why breathing into a bag helps, you are just getting back the CO2 you have lost. 

Hypoventilation = decrease in respiratory rate allows for retention of CO2 so pCO2 goes up so pH decreases = respiratory acidosis 

If you can remember pH = HCO3-/pCO2 you are set, Now plug in some numbers and see what happens with pH. 

Trypansoma cruzi

Protozoa! There are way too many of these things!! Here is a helpful hint to remember 1 of them.

Trypansoma Cruzi = Chagas' disease = cardiomyopathy (cardiomegaly), megacolon, megaesophagus. Predominantly is South America. Transmission = Reduviid Bug. Treat with Nifurtimox

First think of Tom Cruz as Cruzi, he is a megalomaniac (narcissist). Megalomaniac reminds me of Cardiomegaly = the main symptom of the disease. Tom cruzi dated Penelope Cruzi who is from South America which is where this disease is from. Now I am sure if you asked Tom Cruzi about his little outbreak on Oprah he probably wishes he could re-do that show because he made such an ass of himself. So this will remind you that the disease is transmitted by the reduviid bug. As far as the treatment goes well, we all think that Tom Cruzi is a fart so naturally you would use Nifurtimox to treat it.

pumpKin

So I had a practice question about the Sodium - Potassium Pump and what gets pumped out or the cell and what gets pumped into the cell. Since it has been a while I could not recall exactly how it works. So a buddy of mine told me this one:

pumpKin = from this word you can remember that it is K (potassium) that gets pumped into the cell which means it must be Na (sodium) that gets pumped out of the cell. Now I always forget how many of each get pumped in or out.

K+ = 2 letters a "K" and a "+" so that will remind you it is 2 K+ that get pumped into the cell and Na+ = 3 letters "N", "a", "+" so that will remind you that 3 Na+ get pumped out of the cell!

Na+/K+ pump = it pumps 3 Na+ out of the cell and 2K+ into the cell. Think "pumpKin"

Thank you Amit!

Imprinting

Genomic imprinting. The classic example is Prader Willi and Angelman's. Basically imprinting means that you get a different disease for a mutation at the same chromosome depending on who the allele was inherited by. If its moms allele it is one disease and if it is Dad's allele it is another disease. 

Prader-Willi = Willi is a man's name so this reminds me that it is associated with paternal allele inheritance. Some use the P in Prader to remind them of paternal

Angelman's = Angel reminds me more of a woman than a man. (I think of devil when I think of man not angel). So because Angel = women I remember Maternal allele inheritance for Angleman's.

The chromosome affected in these diseases = 15(q11q13) deletion occurs

Prader-Willi = can't stop eating = obesity and diabetes, mentally slow, hypogonadism 

Angelman's = Happy puppet, ataxia and inappropriate laughter, mental retardation.

Glycogen Storage Diseases

So there are these diseases that occur when a person has an issue with their glycogen metabolism. Because they can't process the glycogen it accumulates to toxic levels. There are a bunch but we only need to remember 4.

Type 1 = Von Gierke's

Type 2 = Pompe's

Type 3 = Cori's

Type 5 = McArdle's 

1 and 3 both present with severe hypoglycemia. Type 3 is really a mild version of Type 1 

Type 1 = Von Gierke's = The G in Gierke's reminds me of the deficient enzyme = Glucose-6-phosphatase. The glycogen builds up in the liver giving the patient hepatomegaly and a protruding belly. Severe hypoglycemia usually manifests with seizures. 

Here is how I remember Type 2: When I think of Pompe it makes me think of pompus or megalamaniac which makes me think of cardiomegaly. In Type 2 the deficient enzyme is Lysosomal alpha-1-4-glucosidase (acid maltase) and you get glycogen build up in the heart. Some like to think of Pompe as a pump as in the heart. 

Type 3 or Cori's reminder =  Amy who is 16 knocked Cori off the tree branch.

Enzyme Deficiency = Debranching Enzyme = amylo-1,6-glucosidase. Type 3 is a milder version of Type 1. Gluconeogenesis is still functioning 

Type 5 or McArdle's = M in McArdle's makes me think of Muscle. Type 5 lacks the enzyme muscle glycogen phosphorylase so the patient gets glycogen build up in the muscles and gets horrible muscle cramps.

Type 1 and Type 2 error

Type 1 error (alpha) = Stating that there is an effect or difference when none exists. Mistakenly accept the experimental hypothesis and you reject the Null hypothesis. 

Type 2 error (beta) = Stating that there is not an effect or difference when one does exist. You fail to reject the null hypothesis.

Ok I hate this crap. You read it 10 times and you are still confused! So I came up with a better way to remember these errors. When I think of the numbers 1 and 2 I think of going to the bathroom, Number 1 being urination and number 2 = going poo. Let's start with number 2.

Gamble and lose = this is when you think you have to fart and only fart so you let it go and to your surprise it was more than a fart, it was a fart with some fecal matter also known as a "shart". This is a Type 2 error = You did not think there was anything there but you were wrong there was fecal matter there = Type 2 error = mistakenly saying nothing is there when in fact something is there.

Now for number 1 or urinating. Older men and people with UTI's or bladder infections often experience something called urgency which is the feeling that they have to urinate. So they head to the bathroom to let it flow only to find out there is no urine to flow. So they thought something was there but nothing was really there. This is a type 1 error = think something is there when there really is nothing there. 

Null hypothesis = hypothesis of no difference. You do a study on men and women and their sleeping patterns. The null hypothesis would say that you do not think there will be any difference between the men or women's sleeping patterns. The alternative hypothesis is the hypothesis of difference so the alternative hypothesis would state that there will be a difference in the sleep patterns of men vs women. 

So let's say you do the study and you fall asleep so you miss a big portion of tracking the data. So your results show that there is no difference in the sleep patterns of men and women but had you been awake to record the data properly you would have seen that the women slept much more peacefully and did in fact have a different sleeping pattern than the men. The error here is you are stating that something (differences in sleep patterns) is not  there  when in fact there really is something (differences in sleep patterns) there. Now think of the Shart you are saying nothing is there but in fact there really is something there. You go to just fart but accidently crap your pants! This deals with feces = Type 2 error. I think you got it!

Alkaptonuria

Alkaptonuria = Deficiency of homogentisic acid oxidase in degradative pathway of tyrosine. Results in alkapton bodies which cause urine to turn black when left to sit in a jar or beaker. Connective tissue is black. Benign but can cause bad arthralgias 

Here is how I remember this. I think of a leader or a group called El Capeetan (Alkapton) who became the leader because he he won a pissing competition because his piss was black which impressed his superstitious followers. Because his urine was black people thought he was a real manly man and to keep this image he was homophobic (homogentisic acid oxidase deficiency).

Follicular Lymphoma & CLL

Follicular Lymphoma & CLL = similar CD profiles

Both = CD19 and CD20 = B-cell derived

But here is the tricky part......

CLL = CD5+, CD10-

Follicular Lymphoma = CD5-, CD10+

There are 10 letters in the word "follicular" so you can remember that the one with 10 letters is 10+, so Follicular Lymphoma is CD5-, CD10+

1 NADH = 3 ATP

1 FADH2 = 2 ATP

Intro

Here is my blog to document my next 24 days of study for the USMLE. I just finished my 2nd year of medical school at the Chicago Medical School at Rosalind Franklin University. I take USMLE step 1 on June 24 2008 and Today is May 21st. I am going to post my study concept reminders here. My basic attack plan is read First Aid 3 times. Go through Goljan lectures 3 times and do about 1500 - 2000 total questions on Kaplan Q bank, USMLE World and USMLERx.