MS2_I_PATH

% OF ALL PATIENTS WITH DISEASE PRESENT WHO HAVE A + TEST.

TP/(TP + FN) x100

% OF ALL PATIENTS WITHOUT DISEASE WHO HAVE A NEG TEST

TN/(FP + TN) x100

% OF TIMES THAT THE VALUE (+ OR -) IS THE TRUE VALUE.

ex THE % OF ALL + TESTS THAT ARE TRUE + IS THE +PREDICTIVE VALUE

TP/(TP + FP) x100 = (+)PREDICTIVE VALUE

TN/(TN +FP) x100 = (-)PREDICTIVE VALUE

% OF TIMES TEST GIVES THE CORRECT ANSWER COMPARED TO THE TOTAL # OF TESTS

(TP + TN) / (TP + TN + FP + FN) x100

RATE DISEASE OCCURS IN DEFINED POPULATION.

HAS PROFOUND EFFECT ON PREDICTIVE VALUE OF A TEST RESULT, EVEN IF THE SENSITIVITY AND SPECIFICITY ARE VERY HIGH.

TP = PREVALENCE x SENSITIVITY

TN = (1 - PREVALENCE) x SPECIFICITY

FP = (1 - PREVALENCE) x (1 - SPECIFICITY)

FN = PREVALENCE x (1 - SENSITIVITY)

NORMAL: 4000 - 11,000 cells/mm^3

ELEVATION TYPICALLY DUE TO BAC, BUT CAN BE VIRAL FUNGAL, OR NO INFECTION.

NEUTs GENERALLY ACOUNTS FOR INC WBC.

LEFT SHIFT --> RELEASE OF IMMATURE NEUTs RESPONDING TO ACUTE BAC INF (BANDS, METAMYELO, MYELO). 4-24 hrs AFTER ONSET.

INTRACELLULAR INF NOT CAUSE LEUKOCYTOSIS OR NEUTROPHILIA (SAL, BRUCE, RICK, CHLAM)

2,000 -- 4,500 cells/mm^3

TYPICALLY SEEN IN ACUTE VIRAL INF, OR SOME CHRONIC BAC INF (TB, BRUCE, SYPH)

HIV DURING ACUTE INF OR AFTER AIDS ONSET IS ASSOC WITH LYMPHOPENIA

MONOCYTOSIS (INC MONO COUNT) -- TYPICALLY SUBACUTE AND CHRON INF, ESP WHEN GRANULOMATOUS INFLAM PRESENT (TB, BRUCE, SAL)

CAN HAPPEN WITH PERSISTENT ACUTE PHASE RESP, SUCH AS IN CHRON INF LIKE TB. FROMSYTOKINE MED SUPP OF BONE MARROW FUNC

INF OF BONE MARROW CAN ALSO --> DEC PROD OF RBC AND ANEMIA BY REPLACEMENT OF MARROW WITH INFLAM CELLS

• ACUTE PHASE RESPONSE:
• --ESR -- ERYTH SED RATE
• --CRP -- C-REACTIVE PROT (MORE SPECIFIC THAN ESR)

-- THESE MAY BE ELEV IN SOME CHRON ING (BAC, ENDOCARD, OSTEO) BUT ARE NON-SPECIF BC ALSO ELEV IN OTHER INFLAM CONDITIONS AND NEOPLASTIC

LEUKOCYTES IN URINE --> UTI

PRESENCE OF BAC IN BLD W OR WO CLINICAL DISEASE

1) TRANSIENT -- COMMON OCC IN HEALTHY PEEP BUT BAC ARE CLEARED BY NML HOST DEFENSES, SO NO Sx

2) INTERMITTENT -- FOCAL INF W INTERMITTENT SEEDING OF BLD (LOCAL ABSCESS W INTERMITTENT RELEASE OF BAC INTO BLD)

SYSTEMIC INFLAM RESPONSE SYND

SYST INFLAM MAY BE DUE TO INF OR NON-INF CAUSES OF TISSUE INJURY

SIRS IS IDed CLINICALLY WHEN 2 OR MORE PRESENT:

• 1) TEMP > 38*C OR <36*C
• 2) HR > 90 BPM
• 3) RESP RATE > 20 BrPM OR PCo2 < 32 mmHg
• 3) WBC >12,000 OR < 4,000 OR > 10% BANDS

BROAD DEF FROM INDERSTANDING THAT GEN OF INFLAM MEDIATORS RESULT IN CLINICAL SYND OF MULTI-ORGAN DYSFUNC

SEPSIS -- INF RESULTING IN SYST INFLAM RESP

DOESN'T NEC INDICATE BACTEREMIA BUT IS COMMONLY USED THAT WAY

IMMUNE RESPONSE IS DYSREGULATED --> LOCAL BENEFICIAL EFFECTS BECOME DETRIMENTAL WHEN SPREAD SYSTEMICALLY

SEPSIS OFTEN USED IN PEDS TO REFER TO CHILD WHO MAY HAVE A SERIOUS INVASIVE INF (MENIN, PNEU, UTI etc) OR TO DESC A SERIOUSLY ILL APPEARING INFANT

SEVERE SEPSIS: SEPSIS W ACUTE ORGAN DYSFUNCTION

SEPTIC SHOCK -- SEPSIS W ACUTE ORGAN DYSFUNC (SEVERE SEPSIS) AND HYPOTENSION DESPITE IV FLUID

TOXIC SHOCK SYND -- HYPOTENTION AND MULTI-ORG DYSFUNC RELATED TO INITIATION OF SYSTEM INFLAM RESP BY RELEASE OF TOXINS FROM STAPH OR STREP THAT COLONIZED MUCOSA, OR CAUSING A FOCAL OR SYST INF

• PATH:
• 1) DEC WORKLOAD
• 2) LOSS OF INNERVATION
• 3) ISCHEMIA
• 4) LOW NUTRITION
• 5) LOSS ENDOCRINE STIM
• 6) DUCT OBSTRUCTION

• PHYS:
• 1) LOSS ENDOCRINE STIM (SEXUAL ORGANS)

2) AGING

ALSO LIPOFUSCIN PIGMENT

LOSS OF ENERGY (ATP)

MITOCHON DMG

LOSS OF Ca HEMOSTASIS

DEFECTS IN PLASMA MEM PERM

REACTIVE OXY SPECIES

• REV:
• 1) CELL SWELL --> PALLOR, INC TURGOR & ORGAN WEIGHT

2) ULTRASTRUCTURAL CHANGES --> MITOCHON SWELL,

DILATION OF ENDOPLASMIC RET WITH DETACHMENT OF POLYSOMES,

DISAGG OF GRANULAR AND FIBRILLAR ELEM OF NUC,

LOSS INTERCELL CONTACTS,

DMG OF MICROVILLI,

PM BLEBBING

• BIOCHEM CHANGES:
• 1) CESSATION OF RESP AND ATP DEPLETION

2) INC GLYCOLYSIS

3) IMPAIRED VOL REG THROUGH LOSS OF PUMP ACT AND INFLUX OF H2O AND IONS

4) IMPAIRED SYNTH FUNC

5) DEC INTRACELLULAR pH DUE TO INC LACTIC ACID PROD

CLINICALLY: LEAKAGE OF INTRACELL CONTENTS INTO PLAMA (CARDIAC MSC ENZ CREATINE KINASE MB OR HIGHLY SPEC CARDIAC PROT TROPININ --> CARDIAC INFARC)

1) INC IONIZED Ca WITHIN CELL LEADS TO ACT OF ATPases, PHOSLIPases, PROTases, & ENDONUCases

2) MITO DYSFUNC DUE TO Ca ACCUM

3) LYSOSOMAL DYSFUNC, AUTOPHAGY, AUTOLYSIS

4) PM DMG DUE TO INC PHOSLIPase ACT --> LEAKAGE OF INTRACELL PROTS INTO PERIPH CIRC

5) PRECISE MOMENT OF TRANSITION "POINT OF NO RETURN"

• MORPH FEATURES:
• 1) INC EOSINOPHILIA DUE TO LOSS OF NML BASOPHILIA (RNA) AND PARTLY DUE TO INC BINDING OF EOSIN TO DENATURED PROTS

2) CYTO SHOWS VACULES W MOTH-EATEN APP DUE TO ENZ DIG

3) HOLES IN PM AND ORGANELLE MEMs, MITO SWELLING WITH AMORPH DENSITIES, PHOSLIP (MYELIN FIGs), OTHER DEBRIS

• 4) NUC CHANGES BY LIGHT MICRO USED TO TELL NML FROM IRREV CELLS -->
• --KARYOLYSIS (DNA LYSIS)
• -- PYKNOSIS (NUC SHRINK AND INC BASOPHILIA
• -- KARYORRHEXIS OR FRAG OF PYKNOTIC NUC

LOSS OF MEM INTEGRITY // MEM BLEBBING BUT NO LOSS OF INT

FLOCCULATION OF CHROM // AGG OF CHROM AT NUC MEM

CELL SWELL & LYSIS // SHRINK

DIFF BLEBBING SEEN W COMPLETE CELL LYSIS // FORM MEM BOUND VESCICLES (APOP BODIES)

DISINTEGRATION (SWELL) OF ORGANELLES // NO DIS OF ORG; REMAIN INTACT

LOSS OF ION HOMEOSTASIS // REGULATED; INVOLVES ENZ STEPS

NO ENERGY REQ // ATP DEPENDENT

POST-LYTIC DNA FRAG // PRE-LYTIC DNA FRAG

--PATHOLOGIC PM PERMEABILITY LATE IN APOP. CELL CONSIDERED DEAD LONG BEFORE CYTO ENZs LEAK.

--NEC PRODS INFLAM // DOESN'T

1) COAG -- pH, ENZ

2) LIQUEFACTIVE -- PUSS --> PROTEOLYSIS --> NEUTs RELEASE DIG ENZs WHEN DIE

3) FAT -- LIPOLYSIS (PANCREATITIS)

4) CASEOUS -- USUALLY TB --> LYMPH REPLACED BY NECROSIS

5) GANGRENOUS -- WET OR DRY

6) HEMORRHAGIC

1) DIETARY PROT DEF

2) ADEQUATE CALORIC INTAKE

• 3) CLINICAL:
• --DISTENDED ABD (ENLARGED FATTY LIVER)

• --LIGHT HAIR W GREY BANDS (FLAG SIGN)
• --SKIN LESIONS
• --WASTING OF VISCERAL COMPARTMENTS RESULTS IN HYPOALBUMINEMIA (marasmus shows nml alb)

--WEIGHT LOSS MASKED BY GEN EDEMA (ANASARCA) AND SPARING OF SUBCUTE FAT

1) LOW CALORIC INTAKE

2) BODY WEIGHT < 60% OF NML

3) CLINICAL --> EMACIATED "OLD MAN" APP

4) GROWTH RETARDATION & LOSS OF BOTH FAT AND MUSC MASS

5) SPARING OF VISCERAL COMP WASTING AND THIS ALBUMIN LEVELS ARE RELATIVELY NML --> NO GEN EDEMA

IMPAIRED ARTERIOL FLOW

• 1) PARTIAL ARTERIAL OBST:
• -- CONGENITAL STENOSIS
• -- ACQUIRED STENOSIS BY "ATHEROSCLEROSIS"

• 2) COMPLETE OBST:
• --THROMBOSIS
• -- EMBOLISM

• 3) FUNCTIONAL OBST:
• -- SPASM

IMPAIRED VENOUS RETURN

• PASSIVE OR "PASS VEN CONGESTION": LOCALIZED TO AN ORGAN:
• --VENOUS THROMBOSIS IN ORGAN
• -- LEFT HEART FAILURE --> PULM CONG

• AFFECTING MULI-ORGAN OR WHOLE BODY:
• --PORTAL HYPERTENSION
• -- RIGHT VENT FAILURE --> CONG HRT FAILURE

LEFT: DEC OUTPUT AND RENAL BLD FLOW --> ACTIVATION OF RENIN-ANGIOTENSIN-ALDOSTERONE AXIS --> Na AND H2O RETENTION

RIGHT: INC CINTRAL VONOUS PRESSURE, INC CAP FILTRATION PRESSURE, AND EDEMA

• LIVER:
• 1) HYPOALBUMINENIA

2) INC PRESSURE IN SPLANCHNIC CIRC

3) LYMPHATIC COMPRESSION & OVERLOAD IN SPLANC CIRC

4) DEC GFR & ALDOSTERONISM

• PORTAL HYPERTNS:
• 1) SPLANCH CONGESTION

2) SPLENOMEGALY

3) ASCITES, EDEMA

• HYPOVOLEMIC
• -HEMORR
• --VOM, DIARR
• --BURNS

• CARDIOGENIC
• --MYO INFARCT
• --VENT RUPTURE
• --ARRHYTH
• --CARDIAC TAMPONADE
• --PULM EMB

NEUROGENIC

ANAPHYLACTIC

DEAK

RETINOL - FAT SOLUBLE

• FUNC:
• -VISION
• -MUCOUS CELL DIFFERENTIATION
• -DRUG METABOLISM
• -LIPID MET
• -IMMUNITY

• DEFICIENCY:
• --NIGHT BLINDNESS
• --XEROPHTHALMIA (DRY EYE)
• --KERATOMALACIA (BITOT'S SPOTS)
• --BLINDNESS
• --INFECTION
• --DIARRHEAL DISORDERS
• --MALABSORPTION

• PATHOLOGY:
• --POOR DIM-LIGHT VISION
• --DRY CRACKED MUCOUS MEMs
• --SKIN ERUPTIONS (CORNERS OF MOUTH)
• --DEC IMMUNE FUNC

• TOXICITY:
• --HIGHLY TERATOGENIC!
• --ACUTE --> HEADACHE, DIZZYNESS
• --CHRON--> WEIGHT LOSS, BONE/JOINT PAIN

COMPONENT OF RHODOPSIN --> EXCESSIVE LOSS NECESSITATES REPLACEMENT

• VIT A THERAPY:
• --SKIN DISORDERS (PUSTULAR ACNE, PSORIASIS)
• --ACUTE PROMYELOCYTIC LEUK (abn RARs)
• --INDUCES DIFFERENTIATION IN LEUK CELLS

MAKE IN SKIN FROM 7-DEHYDROCHOLESTEROL

FAT SOLUBLE

• FUNC:
• --Ca & PO4 ABS AND UTILIZATION
• --ANTI-MICROBIAL
• --RANKL PROT

• DEFICIENCY:
• --RICKETS
• --OSTEOMALACIA

• PATHOLOGY:
• --WEAK/DEFORMED BONES
• --INC PHOS FROM DEC Ca

FAT SOLUBLE

• FUNC:
• --?
• --ANTIOXIDANT
• --FREE RAD SCAVENGERS

• DEFICIENCY:
• --NEURO (RARE)
• --?

• PATHOLOGY:
• --ATAXIA
• --MUSC WEAKNESS
• --ABS TENDON REFLEX
• --HEMOLYTIC ANEMIA IN INFANTS

FAT SOLUBLE

• FUNC:
• --BLD CLOTTING

• DEFICIENCY:
• --DEC BLD CLOTTING PROTS (PROTHROMB etc)
• --TENDENCY TO HEMORR

VIT C (ASCORBIC ACID)

B1 (THIAMINE)

B2 (RIBOFLAVIN)

B3 (NIACIN)

B6 (PYRIDOXIN)

B12 (FOLATE)

ASCORBIC ACID -- FAT SOLUBLE

SCURVY -- BLEEDING GUMS, CONNECTIVE TISSUE DEFECTS (CAPILLARY BASEMENT MEMs)

• FUNC:
• --HYDROXYLATION REACTIONS (PROLINE, LYSINE IN PROCOLLAGEN)
• --ANTIOXIDANT; PROTECTS VIT A,E,B12 FROM OX

NOT TOXIC EVEN IN MEGADOSES

COENZYMES IN KEY MET REACTIONS (GLYCOLYTIC AND TCA CYCLE)

DEFICIENCIES MORE APPARENT INT TISSUES HAVING HIGH METABOLIC RATES

THIAMINE

FOUND IN CEREALS & BEANS MOSTLY

ESSENTIAL COFACTOR IN DECARB, TRANSKETOLASES, AND PYRUVATE DEHYDROGENASE COMPLEXES

• DEFICIENCY:
• --BERIBERI
• ----WET: MOST EXTREME. PERIPH EDEMA, CARDIOMYOPATHY, WERN-KORS SYND
• ----DRY: POLYNEUROPATHY, MUSC WEAKNESS, TENDERNESS, FOOT/WRIST DROP, FORMICATION (CRAWLING SENSE ON SKIN), PARASTHESIA (BURNING, TINGLING), NAUSEA

RIBOFLAVIN

ESSENTIAL FOR FAD AND FMN REACATIONS

• DEFICIENCY:
• --SORENESS/BURNING OF LIPS, MOUTH TONGUE, CHEILOSIS (CRACKS AT MOUTH CORNER)
• --CORNEAL VASCULARIZATION; ITCHING OF EYES
• --DESQAM OF SKIN AND SEBORRHEIC DERM
• --ERYTHROID HYPOPLASIA
• --MAGENTA TONGUE

NIACIN -- NICOTINIC ACID AND NICOTINAMIDE

ESSENTIAL FOR NAD AND NADP REACTIONS

• DEFICIENCY
• --PELLAGRA (BURN-LIKE SKIN LESIONS)
• --"4-Ds" --> DERM, DIARRH, DEMENTIA, DEATH
• --LIGHT SENSITIVITY

FOLATE

NECESSARY FOR DNA AND RNA SYNTH

• DEFICIENCY:
• --MEGALOBLASTIC ANEMIA
• --MYELIN DEGENERATION --> NEURAL TUBE
• --HYPERHOMOCYSTEINEMIA

ESSENTIAL FOR OVER 100 KNOWN METALLOENZYMES, DNA, RNA, AND PROT SYNTH, CELL MEDIATED IMMUNITY

• DEFICIENCY:
• --HEMORR DERMATITIS
• --PIT DYSFUNCTION --> INFERTILITY
• --ANOREXIA, LOSS OF TASTE OR SMELL
• --MENTAL STATUS CHANGE