Usmle Exam Slides!!!

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USMLE EXAM SLIDES!!! Tarek Hassouna

Transcript of Usmle Exam Slides!!!

USMLE EXAM SLIDES!!!

Tarek Hassouna

47,XYYPaternal cause @ meiosis II-gamete receiving both copies of one homolog (in this case YY)

Prophase=> crossover

4 chromosomes2 types

2 chromosomes 2 types – All x 2

1 chromosomes 1 types – All x 4

Brachial PlexusBiceps brachialisBiceps brachi

Deltoids

Can not flex elbow!

Cannot ABduct! arm

Cannot extend wrist

Claw hand – lesioned by tauma to heel of hand-fracture of hook of hammate

Nerve innervations of arm

Dr CuMaRadial nerve injury = wrist dropUlnar nerve injury = claw hand Median nerve injury = Ape hand

The hands

Guyons Canal – associated with ulner nerve injury!! - claw hand!!!

Leg compartments Deep posteriorcompartment

Anterior compartment

Unhappy triad

Medial collateral ligament

Lateral Meniscus

Anterior cruciate ligament

A blow from the lateral side of the knee causes a tearing of the medial coll lig. – occurs among foot players

This occurs because of attachment of the lateral meniscus which tears Medial meniscus is associated with the ACL – so that also tears Thus, you get the unhappy triad…

Postnatal derivates fetal remanant

Umbilical vein Ligamentum teres hepatis - falciform ligament

Umbilical arteries Medial umbilical ligament

Ductus arteriosus Ligamentum arteriosum

Ductus venosus Ligamentum venosum

Foramen ovale Fossa ovalis

allantois Urachus – median umbilical ligament

notochord Nucleus pulpos of invertebral disc

Celiac trunk

Common hepatic

Hepatic proper

Right gastric

Spleenic

Left gastroepiploicRight

gastroepiploic

Gastroduodenal

Left gastric

Hesselbach Triangle indirect hernia-internal deep ring-into the scrotum – compresses sperm chord-infants

Direct hernia -hasselbech triangle -medial to epigastric artery-external ring!!!

Rectus abdominis muscle (medially)Inferior epigastric vessels (superior and laterally).Inguinal ligament, sometimes referred to as Poupart's ligament (inferiorly)

Bilateral hemiparisisContralateral proprioception deficitIpsilateral paralysis of hypoglossyl

Contralateral loss of pain + tempIpsilateral-dysphagia-hoarsness -decreased gag reflex-facial pain + temp-trigeminal nucleus -ataxia

Ipsilateral-faical paralysis-cochlear paralysis-Vestibular -facial pain + temp-dystaxia

Contralateral -homonymous hemianiopia with macular sparing-visual changes

Contralateral-face + arm paralysis + sensory loss-aphasia (dominant)-left sided neglect

Medial surface of brain-leg+ foot area -sensory cortices

Most common site of CoW aneurysm!!-visual field defects

Most common site of aneurysm!!-CNIII palsy

Locked in syndrome- CNIII is intact

Nortrptyiline DesipramineImipramine

ClomipramineAmitriptyline

MoA:

Block the presynaptic reuptake of 5HT + NE + DA-increased levels!!!

Treatment /DOC:

Neuropathic pain

Adverse effects!!

Anticholinergic effects!!Orthostatic HypoTNDry mouth + confusion + sedation

Cardiac tox!!

Things to know!!

Impramine – eneuresisNortryptiline – least orthostatic!!Clomipramine – most serotonergic TCA!!

FluoxetineCitalopramSertraline

EscitalopramParoxetine

Fluvoxamine

MoA:

Reuptake inhibitor only for seratonin!!!

Treatment /DOC:

DOC!! – depressionPremature ejeculationBulemiaOCDPanic disorder

Adverse effects!!

NauseaHeadacheDiahrrheaRestlessness + insomnia

Seratonin syndrome

Things to know!!

DOC!!Seratonin syndrome = 2 SSRI + 1 MAO

Fluoxamine – OCD!

TranylcyprominePhenelzine

MoA:

Block the enzyme monoamine oxidase

Treatment /DOC:

Adverse effects!!

Must have tyramine free diet!!

HTN crisis!!-tx with phentolamine + nitropurriside

Things to know!!

tyramine free diet!!

Calculating + interpreting RiskRisk Equation Interpretation

Odds ratio (a/b)/(c/d) = ad/bc Odds of having disease in exposed group vs. unexposed

Relative Risk a/(a+b) / c/(c+d) getting the disease exposed vs. unexposed

Attributable risk (a/a+b)/(c/c+d) DifferenceExposed vs. unexposed

Diagnostic testingDisease (+) Disease (-)

Test (+) TP FP

Test (-) FN TN

Sen => TP/(TP+FN)Spec => TN/(TN+FN)

SNOUT => Sensitivity rules OUT!SPIN => specificity rules IN!

SleepSleep stages description EEG readings

awake Awake + alertActive + mental concentration - Beta waves

Awake but eyes closed - Alpha waves

1 Light sleep

2 Deeper sleep- bruxism

3-4 Deepest non REM sleeepSleepwalking Night terrorBed wetting

REM Dreaming loss of motor toneerections

TachycardiaMore than 100 BPM

Atrial fibrillation

What to know:-uncoordinated-irregularly irregular -upper chambers quiver – bag of worms appearance

Atrial flutter

What to know-coordinated electrical stimulation – regularly irregular- due to a loop of electricity in the upper chambers of the heart.

Supraventricular tachycardia

What to know:-repeated periods of very fast heartbeats begin and end suddenly-Same as paroxysmal SVT

Wolf-Parkinson White

What do you need to know: - extra (accessory) connection- most common causes of fast heart rate disorders (tachyarrhymthmias) in infants and children

Perfusion vs. Diffusion vs. Airway problemsproblem PaO2 PaCO2 pH RR Clincal

presentation

Restrictive – Perfusion defect

FungusProtozoatesCancer Neuromuscular diseases

Decrease-causes pul HTN!!

decrease increase increases SOB!!Pul HTNNarrow S2Loud S2RV hypertrophyS4 sound – increases on inspiration

Inpiratory crackles + alveolar infilitrates – hyaline disease

Obstructive –airwayBacterial!!

Decreased Increases-CO2 retainer!!! – pneumotactic center stimulated!!

decrease increases TachypneaSOB!!

V/q mismatchV/Q PaO2 PaCO2

high Increased – thus perfect environment of tuberculosis

Decreased – since ventilated, Co2 can escape!

low Decreased – no ventilation to that area!!

Increased – no ventilation to that area!!

Antiarrythmics in kids

Ventilatory and ABG patterns in ComaBreathing Pattern

Metabolic Pattern

pH, PaCO2, HCO3

Specific Conditions

HyperventilationHypocapnia => vasoconstriction => decreased CSF formation

CompMetabolic acidosis

pH < 7.3PaCO2 < 40HCO3 < 17

Uremia, DKA, lactic acidosis, acute sepsis, salicylates, methanol, ethylene glycol

HyperventilationHypocapnia => vasoconstriction => decreased CSF formation

Respiratory alkalosis

pH > 7.45PaCO2 < 40HCO3 > 17

Hepatic failure, acute salicylate intoxication, pychogenic causes, sudden onset dyspnea

Hypoventilation Respiratory acidosis

pH < 7.3PaCO2 < 90HCO3 > 17

Respiratory failure from CNS or PNS disease, chest conditions or deformities

Hypoventilation UncompMetabolic alkalosis

pH > 7.45PaCO2 > 45HCO3 > 30

Alkali ingestion. Usually no impairment of consciousness; suspect psychogenicLow volume state!

Toxic SyndromesGroup BP P R T MS Pupil

sizePeris-talsis

Diaphor-esis

Other

Anticholinergic agents

-/ ± Delerium Dry mucous membranes, flush, urinary

retention

Cholinergic agents ± ± -/ - Normal to depressed

± Salivation, lacrimation, urination, diarrhea,

bronchorrhea

Ethanol or sedative-hypnotics

-/ Depressed ± - Hyporeflexia

Opioids Depressed - Hyporeflexia

Sympathomimetic agents

Agitated -/ Tremor, seizure

Withdrawl from ethanol or sedatives

Agitated, confused

Tremor, seizure

Withdrawl from opioids

- - Normal, anxious

Vomiting, rhinorrhea,

piloerection, diarrhea

Goldfrank’s Toxicologic Emergencies, 2006

Glycogen storage diseasesGlycogen Storage disease Enzyme deficiency CP Keywords

Von Griekes Type I Glucose 6 phosphatase Hypoglycaemia Hepatomegaly Hyperlipidemia Failure to grow

Lactic acidocis Hyperurecemia Protuberant bellyXanothomas on buttocks

Pompe’s type II Acid maltase Hepatomegaly Muscle weakness Tendionous Xanthomas!!

Death by age 2Heart failure

Cori’s / Forbes type III Glycogen debrancher Hypoglycaemia Hepatomegaly Hyperlipidemia Causes myopathy

Glycogen debrancher!!!Accumuation of dextrin like structures in cytosol-no fatty infiltration

***Anderson Type IV Glycogen brancher Hepatospleenomegaly Cirrohosis Failure to thrive

Cirrohsis!!!

McArdles type V Muscle glycogen phosphorylase

Excersise induced cramps rhabdomyelosis

Renal failure-dark urine!!!-myoglobinuria

Her’s Type VI Liver glycogen phosphorylase HypoglycaemiaHepatospleenomegaly

Taruis Type VII Muscle PFK Excersize induced cramps Weakness

Growth retardation Haemolytic anemia

Hypernatremia

Hypernatremia

Vascuar

Hypovolemia Main cause!! – if water

is down then Na+ concentration rises

Renal

GlycouriaDiabetes insipdus

Decreased vasopression

Endocrine

Conns syndrome Cushings disease

GIT

Severe watery diahrrea

Hyponatremia

Hyponatremia

Renal

SIADH – increased ADH

Concentrated urine Cerebral edema

GIT

Severe diahrrea Vomitting

Respiratory

Small cell carcinoma

increased H2O retained – oliguria

Endocrine

Increased cortisol – Addisons

CNS

NauseaVomitting Headache Malaise

Cardiac

Lidocaine toxicty – prolonged QT interval –

Na+ channel blocker

Hypercalcemia

Hypercalcemia

GIT

Constipation - hardens feces

CNS

Psychotic noiseDepression Confusion

Cardiac

Short QT interval

Renal

Stones – calcium oxalate

Endocrine

Primary hyperparathyroidism

Lithium use

Respiratory

Small cell carcinoma –PTH secreted!!

Cancer – T-cell leukemia

Name of disease Genetics Enzyme deficient CP/Diagnosis/treatment DescriptionFabrey’s disease X-linked recessive Alpha galactosidase A

Angiokerotomes- tiny painless papules on the body (thighs, buttocks, lower abdomen)Vortex keratopathy -destruction of cornea -but this does NOT affect visionPeripheral NeuropathyCVD’s Diagnosis - fetal amniocentisis- chorionic villus sampling Treatment - enzyme replacement

Deficiency results in the accumulation of globotriacyl ceramide - accumulates in blood and leads to impairment

of the blood vessel system

Goucher’s disease Autosomal recessive B-glucocerebrosidase Hepatospleenomegaly Hyperspleenism- enhanced destruction of RBCs, WBCs, and

platelets => leads to anemiaCirrohsisOsteoporosisBlood work- increased alkaline phosphotase- increased ACE- increased Ig levels Treatment- enzyme replacement- mannose glucocerebrosideMG should be taken 60 units/kg – intravascular IV every 2 weeks

MOST common LSD!!!- also called the “housekeeping” diseaseResults in the accumulation of glycosylceremide - deposits in spleen, liver, kidneys,

bonemarrow and lungs - BUT, for some reason, there is no

abnormality seen in the heart, lungs, or kidney

3 types- Type I => early life – no CNS involvement - Type II => six months- Type III => any age – systemic involvement

Tay Saches Autosomal recessive On chromosome 15

Hexoamidase A-def in alpha subunitIf Bsub – then Sanoff’s disease

Cherry red spots on macula – this is only suggestive!!Optic atrophy Diagnosis - serum levels of hexoamidase should be

low- whirling appearance in slides of tissue- onion skin Treatment - substrate reductase therapy

Deficiency results in accumulation of GM2-gangliosidases Three types- Type I – neonatal- Type II – childhood- Type III – late onset

Neimans Pick disease Autosomal recessive Sphingomyelinase Enlargement of sleep + liverFoamy cytoplasmEnlarged lymph nodesDeath occurs within first year of life

Deficiency of sphingomyelin

Metachromatic leukodystrophy Autosomal recessive Aryl Sulfatase A DementiaAtaxiaTreatment- Bone marrow transplantation- Stem cell transplantation

Deficiency leads to accumulation of cerebroside sulfate

Mucopolysaccharideosis- Hurlers – most severe!!!

Autosomal recessive Alpha-2 iduronidase Corneal ulceration – clouding!!Gargoylism Course facial featuresDevelopmental delayDiagnosis- chorionic villus sampling- amniocentisis Treatment- enzyme replacement- Bone marrow transplant- Umbilical cord transfusion

Deficiency results in accumulation of heparin sulfate + dermaton sulfate

Mucopolysaccharideosis- Hunters

X-linked recessive Iduronate sulfatase Aggreesive “hunting” behaviorTreatment- enzyme replacement

Defiency leads to accumulation of leparin sulfate + dermaton sulfate

Acid base disorders pH = 6.1 log ([HCO3-]/(0.0301)PCO2

pH can be decreased by decreasing HCO3 or by increasing PCO2 pH can be increased by increasing HCO3 or by decreasing PCO2

pH HCO3 PCO2 compensation

Respiratory alkalosis

increased Decreased – by compensation

Decreased Renal-increased excretion of HCO3

Respiratory acidosis

decreased Increased – by compensation

increased Renal-increased NH4 use!

Metabolic alkalosis

Increased Increased Increased – by compensation

Lungs – keep CO2 – hypoventiliation

Hypokalemia Metabolic acidosis

decreased decreased decerased Lungs – eliminate CO2 – hyperventilation

Enzyme kineticscompetitive Non-competitive

Slope (Km/Vmax) increased increased

Y-intercept (1/Vmax) unchanged increased

X-intercept (-1/Km) increased unchanged

O2 binding curve

This occurs at 100% saturation of O2

- When fully saturated, each gram of Hb contains 1.39 mL of O2

This upward spike is due to the fact that the combination of the first heme in Hb and O2 increases affinity for the second, then the third, then the fourth!!

O2 affinity deccreases!!

O2 affinity increases!!

In any case of chronic blood loss – there is less Hb avalible!! – function of it is still normal!!

Valvular disorder – left side of heart!!Murmurs

Increased Ventriclular pressure - >120 mm Hg

Aortic valve

pathology

Pressure gradient b/w ventricular +

aoartic

Aortic stenosis

S4 gallopLVHMidsystolic murmurThrills – radiation to carotixReverse S2 split

No pressure gradient

between vent. + aor.

Aortic regurgitati

on

Hypervolemic/prolapsing pulseEarly diastolic murmurDescendoBest heard leaning forwardVisible suprasternal pulsationsSplit S2

Increased atrial pressure - >15 mmHg

Mitral valve

pathology

Atrial pressure increase at diastole

Mitral stenosis

LHFOpening snapLoud S1Middiastolic Crescendo

Artial pressure increase at systole

Mitral regurgitation

lLHFLaterally displaced apexPansystolic murmurThrils towards the axilla Loud P2PlatoS3 gallop

Valvular disease – right side

Murmurs

Ventricular pressure >25

mmHg

Pressure gradient b/w ventricular +

aortic

Pulmonary stenosis

RHF + Pul HTNJVP – prom A waveParasternal heaveMidysystolic murmurThrill – radiation to left shoulderS2 split

No pressure gradient

between vent. + aor.

Pulmonary regurgitation

Early diastolic murmur

Atrial pressure >5 mm Hg

Atrial pressure increase at

diastole

Tricuspid stenosis

JVP – giant A waveMid-diastolic murmurBest heard on inspiration

Artial pressure increase at

systole

Tricuspid regurgitation

JVP – prominent Y descent JVP – large v waveParastenal heavePansystolic murmur

Increased Insulin

Liver

Carbs

Dec. GNGDec. GlycogenolysisIncreased glycolysis

Increased glycogenesis

Fat

increased lipogenesisIncreased lipolysis

Protein

Decreased breakdown

Fat cells

Carbs

Increased glucose uptake

Increased glycerol synthesis

Fat

Increased FAA syn

Decreased lypolysis

Muscle

Carbs

Inc. glucose uptakeIncreased glycolysisInc. glycogenolysis

Protein

Increased AA uptakeIncreased

protein synthesis

Increases lipoprotein lipase

GlycolysisGlucose

G6P

F6P

F16-BP

F26-BP

Glyceraldehyde-3P

DHAP

Glycerol 3P

1,3 BPG

23-BPG

3PG

2 PG

PEP

Pyruvate

Hexokinase+ GIT

PFK 1PFK II

G6P Isomerase

ATP -> ADP + Pi-ATP, Citrate, Glucogon inhibit PFK1 in high amounts

Aldolase

TriosphosphateIsomerase

G3P dehydrogenaseNAD -> NADH

ATP -> ADP + Pi

Phosphoglyceratekinase

ADP + Pi -> ATP >

Phosphoglyceratemutase

PhosphoenolpyruvateEnolase+ H2O

Deficiency is an autosomal recessive disorder•it affects survival of RBCs because RBCs can only rely on glycolysis and nothing else- treatment – spleenectomy and blood transfusion

Lactate

Lactate dehydrogenase

NADH -> NAD + H+

GalactoseGal-1PGlu-1P

GalactokinaseUridyl transferasePhosphogluco mutase

CP: - vomiting, jaundice, hyperbilremia, hyperglycemia, lethargy, cirrohsisTreatment – eat/drink milk products

FructoseF1P

FructokinaseFructose 1P uridyl transferase

Deficiency in FK-fructoseuria – a hereditary condition CP – vomiting, diahrea, apathy, liver damage leading to jaundice•if it reaches the kidney, you get Fanconi syndrome!•Failure of resorption of fructoseThink of expired drugs – adverse reactions cause this syndromeCP: hypophosphatenemia, renal glycosuria, hypourecimia

HemolyticAnemia

Rate limiting Enzymes!!+ Rate limiting step in Glycolysis

Pyruvate Kinase

ADP + Pi -> ATP >

Deficiency leads to galatosemia + galatosuria •causes cataracts and mental retardation at young ages

AlanineAlanine aminotransferase

Deficiency of alpha 1-4 glucosidase •type II Pompes•type III Cori’s •type IV Anderson’s

Cell trauma

Cell wall release phospholipase

PLC PLA2

20 carbonArachnoic acid

HPETE (hydroperoxyeicosatetranoic acid)

Prostoglandins

Leukotriens

Prostacyclin

Thromboxane

Lipoxygenase

COX1,2

Inhibition of platelet aggregation;vasodilation;

Inhibited by indomethicin

Inhibited by asprinCelecoxib

Inhibited by Cortisol

Leukocyte chemotaxis

Facilitates closer of PDA

Stimulation of plateletaggregation; vasoconstriction

Note: All 3 eicosinoids induce inflammation!!!Redness—An insect's sting will trigger the classic inflammatory response. Short acting vasoconstrictors — TXA2—are released quickly after the injury. The site may momentarily turn pale. Then TXA2 mediates the release of the vasodilators PGE2 and LTB4. The blood vessels engorge and the injury reddens.

Swelling—LTB4 makes the blood vessels more permeable. Plasma leaks out into the connective tissues, and they swell. The process also looses pro-inflammatory cytokines – C5a + bacterial products

Pain—The cytokines increase COX-2 activity. This elevates levels of PGE2, sensitizing pain neurons.

Heat—PGE2 is also a potent pyretic agent. Aspirin and NSAIDS—drugs that block the COX pathways and stop prostanoid synthesis—limit fever or the heat of localized inflammation.

Beta OxidationSource ATP Total

1 FADH2 X 2 ATP 2 ATP

1 NADH X 3 ATP 2 ATP

1 acetyl CoA X 12 ATP 12 ATP

Total 17 ATP

C(2n)(n-1) 14 + 10 -2 = total ATPEx. Palmitate - 16 carbons – C2(8) - n=88-1 x 14 + 10 – 2 = 106 ATP

Source ATP Total

7 FADH2 x 2 ATP = 14 ATP

7 NADH x 3 ATP = 21 ATP

8 acetyl CoA x 12 ATP = 96 ATP

Activation = -2 ATP

NET = 129 AT

Apoproteins Apoprotein Function Deficiency

Apo B APOB "unlocks" the doors to cells and thereby delivers cholesterol to tissues

From Intestine to tissue

Apo B100 => VLDLApo B48 => chylomicrons

High levels => atherosclerosis + heart disease

Low levels => fat mal absorption - because fat cannot be transported!

Apo A Aka HDL - the good cholesterol !

Low levels => atherosclerosis

Apo C Activates lipoprotein lipase- degrades chylomicrons

Low levels – impairs lipoprotein lipase-heparin injection test

Abdominal pain => pancreatitis

Apo E Allows for liver for chylomicrons + IDL to be taken in by liver

triglyceride and cholesterol levels in blood if deficient

Glomerular filtration rateAfferent Efferent

Assessing-RBF-GFR-Creatinine -Inulin

Assessing-RPF-PAH-BUNPrerenal pathologies – results in afferent constriction!!!

-decreased RBF-decreased GFR-increased Creatinine in plasma!!! – why? Because bowmens oncotic pressure is decreased – thus, “sucking power” is decreased!!!

In response -renin -> ang II constricts efferent arterioles-decreased RPF-decreased PAH-decreased BUN in blood

BUT then...turns into renal!!!

Kidney function

Inulin -freely filtered-not secreted -not reabsorbed -freely exrected

PAH-free filtered-free secreted-not reabsorbed-freely excreted

Normally-PGE dilates afferent-increased GFR-increased RPF

NSAIDS INHIBIT THIS!!!

Normally-AngII constricts efferent-increased GFR-decreased RPF

This increase FF!

ACE inhibitors inhibits this!!! – nephrotoxic!!

Renal EquationsParameter Equation Key words

clearance Cx = Ux (Vx/Px) If decreased – mostly reabsorbed

if increased– mostly secreted

Glomerular filtration rate GFR = Ui (Vi/Pi) = Ci

Starling forces GFR = Kf[(Hgc – Hbs) – (Ogc – Obs)] Increased Hbs = >obstructive nephropathy

Decreased Hgs = hypotension

Increased Obs = minimal change disease

Decreased Ogc = hypoalbuminea

Renal plasma flow Upah x V/Ppah Decreased PAH clearance => efferently arterial secretion

Filtration fraction FF = GFR/RPF Decreased RPF = increased AngII - inhibted by ACE

Increased RPF = increased prostaglandins – inhibited by NSAIDS

Water clearance Ch20 = V - Cosm With ADH => CH2O is greater than 0

Without ADH => CH2O is less than 0

Filtered load GFR X Px GFR = Ui (Vi/Pi) = Ci

GFR = exretion rate / Pi = Ci

Excretion rate V X Ux

Left ventricle assessment

Aortic regurgitation– Soft S2

Mitral stenosis – Loud S1

Aortic stenosis– Loud S2

Mitral regurgitation– soft S1

Prerenal vs. Renal problem Etiology Initially after BUN /Cr ratio

Prerenal Renal artery stenosisCHFLow volume state!

Afferent Decreased GFRDecreased RBFIncreased serum Cr

Efferent Decreased RPFIncreased serum BUN

AngII restablishes GFR!

Afferent Increased GFRDecreased RBFdecreased serum Cr

Efferent Decreased RPFIncreased serum BUN

>20

Renal glomerulonephritis, acute tubular necrosis acute interstitial nephritisVancomycin tox!!

Afferent Decreased GFRIncreased serum Cr

Efferent increased RPFDecreased serum BUN

AngII restablishes GFR!

Afferent Decreased GFRIncreased serum Cr

Efferent Decreased RPFIncreased serum BUN

<20

Post renal Urinary tract obstructionBPHKidney stones

Nephrotic syndromeSuspect kidney

disease

Nephrotic syndrome

Proteinuria - >3.5 g/dayHypoalbuminea

Edema Hyperlipideamia

Proliferative

Mesangial proliferative

Lupus + IgA nephro

Endocapillary prlif

Parvo B-19

Membranoprolif

Tram-tracking appearance

Immune complex in mesangium!!

Non-proliferative

Minimal change

Diffuse loss of podocyte foot processes =>

fusion!!

Focal segmental

Only some glomeruli + only

part of it!

Membranous

Immune complex in BM!

Spike + domeSubepithelial

Nephritic syndromeNephritic syndrome

Proteinuria – under 3.5 g/dayHematuria AzostomiaRBC casts

Oliguria – less than 400 mL/day

Type I rapidly progressive

Type II HS

Goodpastures

Linear IF - antiBMPoor prognosisHemoptyisis +

oliguria

Type II rapidly

progressive

Type II HS

Post strep

Lumpy-bumpy

Subepithelial Ics – C3

Children

Diffuse proliferative GN

Wiring loopSubendothelial Anti-DNA Ics in

mesagnium URTI

Acute gastritis

IgA nephro/berge

rs

IC deposits in mesagnium

Type III rapidly

progressive

Wegners granulomato

sis

C-ANCASaddle nose deformitiyPulmonary infections

Microscopic polyangitis

pANCA

Ass. With anti-neutrophil antibodies

Obstructive vs. restrictiveparameter Obstructive Restrictive

Lung capacity Increased OR normal decreased

Residual volume increased Decreased

FEV decreased Decreased

FEV/FVC decreased increased

80% gone? <80% >80%

Cardio equations Parameter Equation Key points

Compliance increase in blood volume in a vessel when the pressure in that vessel is increased

Thus, if pressure increases, compliance decreases => hypertension!!!

Resistance Adenosine => decreased resistance!!!

Cardiac Output CO = SV x HR

CO = rate of O2 consumption/(arterial O2 content – venous O2 content)

During exercise -increased SV-increased CO

Prolonged excerise -increased CO-increased HR – if too high => decreased CO => V-tachy

Mean arterial pressure =CO x TPR=2/3 diastolic pressure + 1/3 systolic pressure

Or

So if pressure increases, so does CO!MAP = SV x HR x TPR-if CO increases, so does SV, HR

AlsoMAP = (EDV-ESV) x CO x HR-the more EDV, the more stroke volume-the more ESV, the less stroke volume

TPR = MAP/COThus, if you increase TPR, you decrease CO!!

Preload = ventricular EDV Increase preload with:-blood transfusion-excersise -excitement – sympathetic

Decrease preload by-venocilators - NO

Afterload =MAP proportional to peripheral resistance

If you increase MAP, you increase after load BUT if I decrease it, with hydralazine => decreased afterload!!

Ejection fraction =(EDV-ESV) / EDV Normally 55%-measuring ventricular contractility – so how much blood is ejected from the ventricle

Urea cycle

Input-HCO3-NH4+

Output-Urea!!!

Key enzymesCarbamoyal phosphate synthase-regulated by N-acetyl glutamate

Deficiences + disease

X-linked Deficiency of this causes hyperammonemia CP:LethargyHyperventilationVommiting + Seizurues + Hepatomegaly Coma -> Death

Increased orotic acid production => def of ornithine transcarboxylase

Phenyl alanine

InputPhenylalanine

OutputTyrosine DopamineCatecholaminesMelalin

Key enzymes

Phenylalanine hydroxylaseHG oxidase

Deficiences + disease

Deficiency of Phenylalanine hydroxylase leads to PKU – its an acquired disorder!!

-CP:During birth, child is normal if its untreated child may develop

mental retardationloss of motor controlautistic symptomspale skin white blond hairmicrocephalyincreased levels of phenylalanine decreased social interactionverbal/non-verbal communication problemsobsession mousy odour!!!

Treatment – semisynthetic diet with reduced phenylalanine but because its essential, patient should take small quantities Aspartame – nutrasweet – should be completely restricted from diet for life!!Women who do not take enough Phe during pregnancy have a high risk of having a child with - microcephaly- mental retardation of child -low birth weight

Deficiency of HG oxidase leads to Alcaptonuria its results from the accumulation of HGincreased excretion of HGif patients urine is exposed to air, it turns dark colored CP: Ochrosis its an autosomal recessive disorder results in pigmentation and calcification of bones and cartlidge – leads to arthritis

Tryptophan

Inputtrytophan

OutputSeratoninMelatoninNicotinate

Key enzymesNone we need to know

Deficiences + disease

Hartnups disease!!-defect in the reabsorption of the AAs in the kidney – one of them is tryptophan!!-Pellegra like sympotomes Diarhhea Depression Dermatitis Sometimes cerebellar ataxia

Tryptophan

BCAs

InputBCAs

OutputHMG CoAAcetyl CoA + Propionyl CoA

Key enzymes

2-ketoacid dehydrogenase complex of enzymes

Deficiences + disease

Maple syrup urine diseaselethargy, dehydration, and vomiting-hypotonia-dramatic weight loss-ketoacidosis (if untreated)- eventually leads to coma and death There are 5 types:-classical MSUD *** MOST SEVERE-Intermediate MSUD-Thiamine responsive MSUD-Enzyme responsive MSUD w/ lactic acidosis

Propanoic acidemia-deficeny in propionyl CoA carboxylase = met. Acidosis, dehydrtation -accumulation of propanoic acid -drives formation of acetyl CoA to the formation of ketone bodies

BSA disease hypoglycemia Ketoacidosis

MUSD increased Increased

Propanoic acidosis increased Increased more!-drives formation of ketone bodies form acetyl CoA

Methylmalonyl CoA acidosis

Increased more!

-inhibition of pyruvate carboxylase + gluconeogenesis by methylmalonyl CoA

Increased more!-accumulated methylmalonic + propanoic acids

Genetics USMLE problem

Population

Carriers

Find pFind q

Find F(Aa) = 2pq

Subtract patient + subtract diseased

Affected

Find F(aa) = q^2

Children

Find ratio of affected vs. Non-

affected

If both conditions – multiply with

carrier prob

If either one condition, add

with carrier prob

Genetic diseases Disease

Autosomal

recessive

Metabolic disorders + steroid synthesisHemoglobin ADA defient SCIDComplement deficiencies Cystic fibrosis

Autosomal

Dominant

Trinucleotide repeats

Spinocerebellar ataxia

Huntingtons disease

Myotonic dystrophy

Cancer

Retinobalstoma – Rb gene

Li – Fraumani = p53

FAP = APCHNPCC = PMS,

MSH, MLHBreast cancer =

BRAC1 Renal clear cell

= VHL

Collagen

Ehler-Danlos Osteogenisis imperfecta

X-linked dominan

t

Vitamin D resistant rickets

X-linked recessive

Lesch – Nyhan syndrome

Hunters + FabreysG6PD

HemophiliasMost

immunodeficiencesFragile X + Rett

syndrome Duchenne + Beckers Muscular dystrophy

Increased paternal age => achondroplasia Increased maternal age => Downs syndrome

Autosomal dominant diseasesAutosomal dominant disease Chromosome/gene KW

achondroplasia FGF recptor 3 Head and trunk are normal sizeAdvanced paternal age

AD polycystic kidney disease Chr. 16APKD1

Always bilateral Berry aneurysmsInfantile form is recessive

Familial adenomatous polyposis Chr. 5 APC

More than 100 polyps!!- 100% carcinoma

Familial hypercholesteremia – type II A LDL receptor Tendonous xanthomas => achillis tendon

Hereditary hemorrhagic telangectasia ? Ass. With atriovenous malformations

Herediatry spherocytosis Spectrinankyrin

Hemolytic anemiaIncreased MCHC

Huntingtons disease Chr. 4Trinucleotide CAG repeats

Decreased levels of GABA + Ach

Marfans syndrome fibrillin Subluxation of lensesDissecting aortic aneurysms Floppy mitral valve

MENs Ret gene => type IIA + IIB Type I => zollinger syndrome - PTH stimualtes histamine releaseType Iia => pheo + medullary CA + parathyroid hypoplasiaType IIIa => pheo + med CA + mucosal neuromas

Neurofib type I Chr 17 Café au lait spotsLinch nodulesNeural tumors

Neurofib type II Chr 22NF#

Bilateral Acoustic neuromas

Tuberous sclerosis Incomplete penetranceVariable presentation

Ash leaf spots

Von hipple-Lindau VHL geneChr. 3

Hemangioblastomas of retina, cerebellum, Bilateral renal cell carcinoma

Lab technique – strep vs. staphBacteria

Catalase (+)

Coagulase (+)

Staph Aureus-yellow + beta hemolytic

-Mannitol (+)DNAse (+)6.5% NaCl

Coagulase (-)

Novobiocin (+)

Staph epidermis

is-others!!

Novobiocin (-)

Staph saprophyticus

Catalase (-)

Hemolysis

Alpha

Optichin (+)

Bile salt (+)

Strep pneumonia

Optichin (-)Bile salt (-)

Strep viridins

Gamma

Bile Esculin (+)

6.5% (+)

Entercoccus

6.5%(-)

Group D S. Bovis

Beta

Bacteracin sen

Group A Strep.

Pyogenes

Bacteracin res

S. Aglatactai

e

Capsulated bacteriaOrganisms

Strep pneumonia

Klebsiella pneumonia

Bacillus anthracis

Haemophilus influenza B

Pseudomonos Aerug

Neisseria meningitis

Cryptococcus neoformans

Common causes of meningitis Newborn (0-6 months)

Children (6 months – 6 years)

6 – 60 years 60+

Group B strep S. pneumonia S. pneumonia S. pneumonia

E. Coli N. Meningitis N. Meningitis N. Meningitis

Listeria H. Influenza Enterovirus Listeria

Viral Protein synthesis

(-) RNA

RNA dep RNA Pol

Reverse transcriptaise

(+) RNA

Translation

RNA dep RNA Pol

RNA

Reverse Transcriptase

cDNA

mRNA

DNA-dep DNA Pol

DNA

DNA dep RNA Rol (host)

mRNA

Structural proteins

How retroviruses (HIV) does it!

HIV virus Gene Proteins Function

Env GP160GP120Gp41

GP120 – mediates CD4 + chemokine co-receptor binding GP41 – mediates fusion

Gag P17P24P7.9

P17 – matrix proteins that stabilizes envelopeP24 – capsid – used for serology!!P7.9 – nucleocapsid associated with RNA

pol Reverse transcriptaseIntegrase Protease

RT – produces dsDNA provirus Int – proviral dsDNA integration into host cell Protease – cleaves polyproteins during assembly process

TAT Transcriptional activator Upregulates transcription

REV Regulator of virion protein expression

Viral replication

NEF Regulatory factor Negative regulator factor

Virus reviews – key USMLE ones!!!Virus Lab Keywords

Parvo B19 ssDNA – smallest!!NakedIco

Kids – rash – slab of cheek!! – red + blotchy!!Fetal hydrops fetalis!!!+ acute polyartrhitis

Measles - Rubeola ssRNA (-) Enveloped Helical Segmented!!

Koplick spots!!!Rash – red+flat+slightly bumpy – spreads down from head to shoulders

Polio ssRNANakedAcid resistant!Divides in enucleated cells!!!

Paralysis + gastroenteritis

HPV 16 +18 NakeddsDNAIco

Cancer in sexually active smoker

Mumps ssRNA (-) Enveloped Helical Segmented!!

Parotitis OrchitisMake infertility

Rubella ssRNA (+)EnvelopedIco

Cataracts leading to blindness in newborns PDA!!

Varicella zoster dsDNANakedTegemented!!Tzmack smear!!- see Cowdry type cells!!

Vesicular lesions in dermatomal pattern

CMV dsDNANakedTegemented!!

Acute retinitis in AIDS patients

HPV 6+11 NakendsDNAIcoCircular!!!PAP smear Koilocytic atypia!!

Gentical warts

HSV 2 dsDNANakedTegemented!!

Painful genital vesicular lesions

Hep E ssRNA Naked

FeverAbdominal painVomittingDiahrrea High mortality in pregnant women

Rabies ssRNA (-) Enveloped HelicalBullet shaped!!

Encephilitis following animal bite – intracellular negri bodies in neurons

EBV dsDNANakedTegemented!!-t8-t14

Teen with fatigue spleenomegaly, atypical lymphocytosis, (+) heterophil Ab test

Norwalk Gastroenteritis on cruise ship

Coronavirus ssRNA (+)EnvelopedHelical

Runny nose-common cold

RSV ssRNA (-) Enveloped Helical Segmented!!

Rapid shallow breathing = brochiolitis!!

Hanta ssRNA (+/-) – only ambisense!!!Enveloped Helical

Hantavirus – pulmonary edema- fever, muscle, aches, increased WBC, low platelet counts - ARDS

Fungus Lab Keywords

Pneymocystis jiroveci Silver stain (+)Bactrim (-)“Hat-shaped cyst

HIV patient – CD4 count <200

Candida albicans Germinal tubing!!!Culture - budding yeast + septatedIn you – pseudohyphae

Thrush = cancer patient on chemo

Crypto. neoformans Visualize with india ink!!Capsular antigens in CSF – latex agglutination Urease (+)!!

HIV = meningitis!!

Histoplasma capsulatum Oval yeast cellsSeptated hyphaeTuberculated macroconidia urine antigen

Lung granulomas - Ohio river valleyIntracellular yeast!!Macroconidia

Microsporium -Trichosporon beigelii – hair shafts!!-Trichophyton mentagrophytes – scalp-

Ringworm!!Wood lamp visualization!

Tinea curis, capitis and pedis

Coccidiodomycosis Spherule w/ endospores Lung granulomas – San Joaquin valley

Aspergillus True hyphae!!!-septated with branches – acute angles 45 degees

Fungus ball in lung!!-angioinvasive

Blastomycosis Broad based budding yeast!! Systemic mycosis -lungs + bone + skin Microconidia

Sporothrix Cigerette shaped!!Resembles a daisy flower

Ascending lymphadenitisRose gardening!!!

Mucormycosis Non-septated!!90 degree branching!!

Rhinocerebral infection Diabetic ketoacidosis

Malaria treatment Plasmodium Primaquine Chloroquine Quinine Mefloquine

Vivax Yes – in the liver

NOPregnancy

Pregnancy Prophylaxis – if res to chloro

Ovale Yes – in the liver

NO – resistantPregnancy

Pregnancy Yes – if resistant to chloro

Malarae NO Yes + primaPregnancy

Preganancy Prophylaxis – if res to chloro

Falciparum NO NOpregnancy

IV – if cerebral + pregnancy

Prophylaxis – if res to chloro

Teratogenic DrugsDrugs Effects

ACE inhibitors nephrotoxic

Alcohol Fetal alcohol syndromeMental retardation

Alkylating agents - anticancer drugs!!-cisplatin-cyclophosphamide-procarbazine

Absence of digits

Aminoglycosides -streptomycin-neomycin-gentamycin

CN VIII toxicity = > ototoxicitynephrotoxicity

cocaine Fetal additionFetal development Placental abruption

Diethylstilbestrol Vaginal clear cell adenocarcinoma

Folate antagonists-methotrexate-sulfamethoxazole + trimethaprim

Neural tube defects

Iodide Hypothyroidism - congential goiter

Lithium Ebstiens anomaly -atrialized right ventricle

Maternal diabetes Caudal regression syndrome – anal atresia RDS?

Smoking (nictotine, CO) Preterm labor + placental prolems IUGR, ADHD

Tetracyclines Yellow teeth

thalidomide Limb defects

valproate Inhibition of intestinal folate absorption

Vitamin A excess High risk for spontaneous abortion + birth defects + cardiac abnormalities

Warfarin Bone defectsFetal hemorrhage abortion

Anticonvulsants-carbamazepine

Spina bidfida

P450 inhibitorsDrug indication Often combined with to become toxic

ritonavirindinavirnelfinavir

Protease inhibitors for HIV infection NNRTIefavirenznevirapineEtravirine=>become toxic ! -

erythromycintelithromycinclarithromycin

Macrolides – 50S inhibitorpreventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex

SivastatinErgot drugs - migraineVerapamil

fluconazoleketoconazoleItraconazole

Anti-fungal agents Warfrin

Verapamil – works on heart!! Ca2+ channel blocker -arrythmia + HTN -varient angina - vasospastic

Warfrin ErgotsPPIszoplicone

Chloremphenical 50S inhibitorpreventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex – prevents peptide bond formation

Not really used drug-cuases grey baby syndrome

Cimitidine H2 receptor blocker-GERD + peptic ulcers-Zollinger Ellison

PPIOpiodsChemotherapy – dox + etop + vin blast + vincris

Amiodareone Antiarrythmic Class III– K+ and Beta blocking action

WarfrinSildenafil ProcainamideDigoxencyclosporine

P450 inducersDrug indications Will inactivate the

following drugsphenytoincarbamazepineoxcarbazepine

Anticonvulsants BDZSex hormone agonists + antagonists SSRIs

Phenobarbitol For Fibrile seizures!!! BDZ

efavirenznevirapineetravirine

NNRTIs for HIV PI’s

rifampin Tb infection

St.Johns Wort Major depression

Grisofulvin Antifungal/bacterial

pioglitazone Oral hypoglycemic -peroxisome proliferator-activated receptors

Epileptic drugsDrug MoA First line for

Phenytoin Na+ blocker Partial tonic-clonic

Carbamazepine Na + blocker-results in decreases SHFRF

Tonic –clonicTrigeminal neuralgia

Valproate Type T Ca2+ blocker-inhibits GABA transaminase – increases [GABA]!!

Myoclonic BUT – can be used for treatment for ALL types of sieuzures

Phenobarbital Increases action of GABA-A-They also block glutamate receptor excitationHigh dose – blocks K+ + Na+ channels

Febrile seizures

Diazepam + lorazepam Facilitates actions of GABA-results in hyperpolarization of the membrane

For acute status epilepticus

Platelet vs. Coagulation

Bleeding disorder

Platelet

Lab- inc. bleeding

time -decreased

platelet count

Bernar Soulier

Decreased PC

Increased BTDecreased

GpIb

Glanzmann

Normal PCIncreased

BTDecreased GpIIb/IIIa

Idiopathic TP

Decreased PCIncreased BT

Megakaryotcytes

Anti-GpIIb/IIIa

Thrombotic TP

Decreased PC

Increased BT

Pentade!!

Coagulation

Factor VII def

Increased PTNormal PT

Hemophilia A

Factor VIII

Normal PT

Increased PTT

Hemophilia

BFactor

IXNormal

PTIncreased PTT

Vit. K def

Factor II, VII, IX, X

Increased PT

Increased PTT

Mixed

Von Willibrand

Increased BTNormal or increased

PTT

DIC

Decreased PC,

everything else

increased!!!

Ristocetin test!

Make slide on thalassemia

gene desc anemia

-a/aa Single gene absent Silent carrier

-a/-a Two genes absent Mild anmeima

--/aa Two genes absent Mild anemia – but more fatal for next generations -> death inutero

--/-a HbM Moderate anemia

--/-- HbBart present – all 4 genes absent Severe anemia

Respiratory curves

Obstructive-COPD, asthma

Restrictive-pulmonary fibrosis-Pneumoconisosi-ALL neurmuscular disease!!!

MixedEmphysema!!-centri = smoking-pan = a1at def

Coombs test

Coombs test

Direct

RBCs with IgG antibodies

Combines with rabbit anti-IgG

If agglutinates => Hemolytic anemia

Indirect

Add test blood O RBCs to test tube of IgG antibodies

Combines with rabbit anti-IgG

If agglutinates => erythroblastosis

fetalis

Different types of immunity

Immunity

Active

Natural

antigen enter + the antibody is

made

Artificial

give antigen body makes

antibody Life-long

immunity!!!!Ex. Polio

vaccine- life-long!!

Passive

Natural

Antibody is given

Mom to fetus - IgA

Artificial

give immune serum – or the

actually antibody

antivenom

Hypersensitivity reactionsHS type Source mediators Discription ClinicalsType I IgE-mediated Basophils

Mast cellsHistamineBradykinin IgETNFIFN gammaPLA2

Initiall exposure-body sees antigen -> B-cells -> increase in plasma cells -> antibodies from IgE 2nd exposure-ab is already formed-it binds to mast cells + basophils First get degranulation-primary mediators – heparain, histamine, proteases-cytokines – TNF, IFN gamme, IL-1-phospholipase A2 – prostaglandins + LTB4

Anaphylaxis

Type II Complement dependentADCCAb mediated cellular dysfunction

MAC complexC3a + b - opsininC5a

Comp dep-Lysis – Ag+Ab -> stimulates complement system + disrupts membrane integrity by forming pores -Opsinins – fixed complement coats Antigen with Ab – enhances phagocytosis

ADCC-IgG coats -> non-sensitized cells destroy-for worms and tumors-facilitate the killing of insulin-producing cellsAb mediated-Ab against surface receptor + changing their function

ADCCParasitic infectionTumorsType II diabetes M – juvenille!Pernicious anemiaCellular dysfunctionMysinia Gravis – DDx- lambert eaton – defect in release of Ach from neuronGraves diseaseWegner’s granulomatosis-antibodies against proteinase 3 – patch necrosis of BVsP.ANCA – Ab against myeloperoxidasePemphigus – Ab attack desmosomes – lung hemorhagesComplement dependent-transfusion-erythroblastosis fetalis-autoimmune haemolytic anema-Drug reactions

Type III Ag+ Ab complex Complement proteinsIgG + IgM

Induced by Ag/Ab complex that produced tissue damage!!! – because they activate complexes -circulating complexes -> produces damage because they deposit at sites of tissues => attract neutrophils + macrophages-in-situ complexes – attach to FC receptor on polymorphs – release cytokines attract PMN + initiate MORE complex - > more complement fixation!!1st stage – formation of Ag/Ab complex2nd stage – deposited complexes in tissue3rd stage – inflammatory reaction!!

Generalized – serum sickness- Amyloidosis- sarcoidosisLocal – arthrus reaction- bacterial – actinomycets –

causes lung + brain abcessacute transplant rejection

Type IV Cell mediated CD4- TH-cells - TNFIFN gammaIL-1macrophages

Characterized as granulomatous inflammation – chronic!

Poison ivy – contact dermatitisTuberculin sensitivityHistoplasmosisSacrcoidosisMS

Wound healing

characteristic 1st intention 2nd Intention

Duration Faster Longer

Pattern More planned – surgery injury More chaotic – crush injury

contracture Less - More contracture

Fibroblast activity Less - Fibroblast activity is more

Susceptibility to infection Less - More susceptible to infection

Surface Can be replaced Surface is defective

Inenstiy Less - more intense

Granulation Less - Larger amount of granulation

Scar Small scar - Larger scar is formed

Weird syndromes Disease Neuro BV Renal Skin

Von Hipple Lindau Retina Cerebellar

Capillary hemangiomas Cystic renal that could complicate to Renal cell carcinoma

Von reckling Houson-chr. 17

PNS tumorsOptic nerve gliomas

Pigmentation of irisCafe au lait spots

NF type II-chr. 22

Acoustic neuromasmeningiomas

Sturge Weber Mental retardationSeizuresHemiplegia

Facial Leptomeningeal

V1 + V2 of trigeminal

Osler Weber TelengectasiaEpstaxisGI bleeds

Tubulosclerosis seizures Cutaneous angiofibromas Renal cystsLiver cystsPancreatic cysts

Ash leaf spots

Penile soarsPenile Soars

Painful

HSV-2

FeverHeadacheMyalgiaVesicular!!

Hemophilus Ducreyi

Inguinal lymphadenopatthy

Painless

Treponium – Syphilis – 1st degree

Painless chancre

Chlamydia

L1-L3 – painful lymphadenopathy

-ABC – african, blindness, chronic infection

Alveolar pressure vs. Intrapleural pressure

Conditions Transpulmonary pressure

Alveolar pressure Pleural pressure

Physiological Always (+)!!! + during inspiration(-) During expiration

(-) 5

Pneumothorax 0 +1 +1

Transpulmonary = alveolar – pleural

1) Any lung volume - transpulmonary pressure is equal to and opposite to elastic recoil pressure of the lung

-thus, if elastic recoil pressure is (+) on exhalation, TP is (-)

2) Inhalation – lung volume pressure (inhalation) < lung volume pressure (exhalation)Exhalation – lung volume pressure (inhalation) > lung volume pressure (exhalation)

SA node graph

Digoxin-directin inhibtions of Na/K ATPase = increased Ca2+ inside cells – increases contractility Esmolol- Class II

-decrease Ca2+ currents-decreases slope of phase 4-increases PR interval

Adrenal physiology Cholesterol

Pregnolone

Progesterone

11 – DOC

Corticosterone

Aldosterone

17 OH preg

17-OH Progesterone

11 Deoxycortisol

Cortisol

Dehydroepialdosterone

Androstenodione

Testosterone

DHT

21

11 11

17

18

17

21

17 OH def => Hypertenion, decreased androgen synthesis21 OH def => Hypotension, increased androgen synthesis11 Oh def => Hypertension, increased androgen synthesis

Normal Adult DiahrreaWhole blood loss

Excessive infusion of normal saline

DiureticsAddisons 21-OH deficiency

EdemaRHFCirrhosisNephrotic syndrome

SIADHInc. H2O consumption

Osmotic diuresisSweating

Diabetic InsipidusFever

Antibiotics Inc. HCO3

[Drug] plasma vs. Time

[drug]plasma

Time

Drug X

Drug Y

measurement Drug X Drug Y

Vd decreased increased

Cl decreased increased

Cl = rate of elim / [drug]Vd = rate of elim/ [drug]Ke

Prader Willi vs. AngelmanMaternal Paternal

Deleted Imprinted Deleted Imprinted

Prader Willi -Chr. 15

Yes Yes

Angelman-Angelman

Yes Yes

Galactose metabolism?Enzyme Clinical presentation Accumulation

Galactokinase K for cataracts!!!-galactosemia-no smile

Galactol

Uridyl transferase JaudiceHepatomegaly Mental retardation

Galactol

B-galactosidase Abdominal distentionDiahrrea

UDP galatose

ANP production

Hypertension

ANP release in response to

increased pressure

Atria

Increased blood volume?

Kidney-decreased

reabsorption of Na+ H2O

Ventricles

Due to LV hypertrophy due to

HTN

Lab values – Renal parameter Normal Value

BUN 10-20

Cr 1

Na+ 135-145

Cl- 98-108

K+ 3.5 – 5.5

HCO3 24

PCO2 40

P02 60-90

Glucose 70-100

P-Osm 300

U-Osm 350-450

P- 2-4

Mg 2-4

Ca2+ 8.8-10.8

PCT(85%)Luman Plasma

H+

HCO3

H2O +CO2 H2O + CO2

H + HCO3 HCO3

Na + Cl- -> NaCl + 2K+ Clinicals-Alkalosis => low volume state-Dehydration => increased Na resorption + increased HCO3

Acetazolamide -> induces RTA II-treatment for increased ICP

Fanconi syndrome + Tetracycline => low energy state => S3 + cardiomegaly

CA

CA

PO4 3-

Na +

Ca 2+

Mg 2+ + AA + Glu

Fanconi protein

Loop of Henle – ascending Luman Plasma

Na

K

Mg

Ca

Cl- What to know:

1) Decreased urine Osm – diluting portion -

2) Furosemide, Toresemide, Butemide, Ethrynic acid

3) Barters syndrome!! – defective Na+/K+ ATPase – thus – hypomagnesmia + hypocalcemia

Gymnastics + Aneorexia + Bulemia

DCT lateLumen Plasma

K+

Na+

Ca2+

Aldosterone

PTHVit.DATPase

Clinical notes -Thiazides that act here cause hypokalemia How? – Low volume state – response is to increase aldosterone – results in hypokalemia!

Collecting ducts!!!

K+/H+ exchange-collecting duct – plasma to cells

HCO3!!!!-major source of bicarbonate absorption

Urea cycle-NH3 Glutamine -> NH4 +

Glutamate

Glutamate -> alpha KG + NH3

80% of H+ comes from here

Asprin OD

Early • Respiratory alkalosis

Later• ASA gets absorbed• Results in met. Acidosis +

Resp. Alk • pH is NORMAL!!!

Increased absorption of ASA• Mixed acidosis => you

are ingesting more acid and retaining more CO2

Renal tubular acidosisRTA Urine pH K+ Notes

I increased decreased Stones!! Ca2+Disfunctional K+/H+ channel @collecting duct

II Decreased decreased PCTDec. HCO3 resorption

III Normal decreased Inherited Carbanhydrase deficiency

IV decreased increased Decreased aldosterone response

Collecting ducts Lumen Plasma

Na+

K+

K+

Na+/K+ exchange

Aldosterone

H+

Clinical-increased aldosterone => Alkalosis – thus, spirolactone can induce acidosis!!!

Vagnial bleeding

Woman

Vaginal Bleeding?

Placenta abrupta – if pregnant

Painless!!!

Endometrial carcinoma

Postmenapausal

Ectopic pregnancy

Pain!!

Hydaform mole

Increased Beta HCG

Dexamethasone suppression testGive Dex

Low dose

Decreased cortisol

Healthy!!

Still increased cortisol

High dose

Decreased cortisol

Pituitary Cushings

Increased cortisol

Increased ACTH

Small cell carcinoma

Decreased ACTH

Tumor of the adrenal

Inhalation vs. ExhalationTP AP IP

Inhalation More (-) 0 to -1 to 0 -5 to -8

Exhalation Less (-) 0 to +1-due to elastic recoil

-8 to -5

Joint pathologyJoint pain?

Erosive

1 joint

Asym

Goutpseudogout

Multiple joints

Asym

ReitersLyme

disease

Sym

B-19 infectionRheumatic feverRheumatoid arthritis – hours!Osteoarthritis - <30 mins + distal joints

Non-erosive

SLEFibromyalgia

Platelet vs. CoagulationBernard SoulierPT – normalPTT – normalPC – decreasedBT – increasedKW:GpIbadhesion

GlanzmannPT – normalPTT – normalPC – normalBT – decreasedKW:GpIIb/IIIaNo clumping!

ITPPT – normal PTT – normalPC – decreasedBT – increasedKW:Megakaryotcytes!

TTPPT – normal PTT – normalPC – decreasedBT – increasedKW:Pentade! – feverHUS

Hemophilia – factor VIIIPT – normalPTT – increasedPC – normalBT – increasedKW:-Xlinked recessive-hemarthrosis

VWFPT – normal PTT – normal OR increasedPC – normalBT – increasedKW:ADRistocretin test!

DICPT – increasedPTT – increasedPC – decreasedBT – increasedKW-trauma + spesis-shistocytes-fibrin split products

Vit K. Def PT – increasedPTT – increasedPC – normalBT – increasedKW-general-protein S + C

MI evolution 0-4 Minimal change -> reprofusion injury

4-12 hrs Edema + hemorrhage

12 hrs – 1 day Coagulation necrosis

1 to 5 days neurtophils

5-10 days macrophages

10-14 days Granulmoas + neovascularization

2 weeks to 2 months Scar formation

GnRH hormonesGnRH

FSHLH

androgens

estrogen

aromatase Ovaries

Progesterone Beta-HCG

Increased in:-ectopic pregnancy-hyditaform moleParital = 69XXXComplete – syn + cyto

Increased in: POS!!!-endometrial carcinoma – adenosquamous CA – MC!!-CP – postmens bleeding-papillary adeno – mets to lungs

-

Motor CNs

Efferent

General

Visceral

SweatSalivaGutPupil contriction

Somatic

Muscle of eyeMuscles of tonge

Special

Visceral

TongueMasticationSwallowing

Facial muscles

Somatic

NONE!

Sensory neurons

Afferent

General

Visceral

PalateCarotidSinustongue

Somatic

Pain + temp in face + ears

Special

Visceral

Tastesmell

Somatic

Vision Hearing

Equilibrium

Heart murmursValve Systole Diastole (early) Diastole (late)

Pulmonary + Aortic MiddleStenosis-left shoulder => pulmonary-Apex to carotid => Aoartic

Pulmonary regurgitation

Aortic reguritation

Tricuspid + mitral Holo/Pan=> Reguritation

Tricuspid stenosis Mitral stenosis

Normocytic anemia

Non-haemolytic

ACDAplastic anemiaKidney disease

Hemolytic

Intravascular

Intrinsic extrinsic

Extravascular

Intrinsic Extrinsic

PNH Autoimmune coldMechanical traumaAortic stenosisProstethic valve

SpherocytosisG6PDPK defSickle CellHbC defectAutoimmune - warm

DIC TTPHUSInfectionMethyl DOPAPenicillin

S1 Split-Baroom BoomRBBB

S2 Split (reverse)-Boom BaroomLBBBAortic stenosisIHSS

S3 sound (Bell)Boom – Ba – Boom – increased elastic limitCHFMitral regurgitationDilated cardiomyopathy

S4 sound-Bell apex – gallop“Baboom-Boom”-non-compliant ventricleAortic stenosis + LVH

If you hear... Then its Due to: KWs

Holosystolicblowing

Mitral regurgTricupsid regurgVSD

Ischemic heart diseaseMitral valve prolapseLV dilation – dilated cardiomyopathy

Squatting on hand grip!!!Kids!

Midsystolic Ejection murmur

Aortic stenosis Age related calcificationBicuspid aortic valve

calcification

MidsystolicClick

Mitral valve prolapse

Marfance sydromeAss. With infective endocarditisRheumatic fever

Squatting on hand grip!!!

BlowingHigh pitcheddiastolic

Aortic regurgitation

Rheumatic fever Syphalis!!

Opening snap Rumbling

Mitral stenosis 2ndary rheumatic fever – buttonhole – fish mouth

Machinary like murmur

PDA child