USMLE KNOWLEDGE

USMLE KNOWLEDGE
→ RECURRENT PSEUDOMONAS AND STAPH PNEUMONIAS,
CHRONIC BRONCHITIS, BRONCHIECTASIS
CONJUNCTIVAL AND CORNEAL LESIONS
ARE MORE SERIOUS COMPLICATIONS THAT
CAN LEAD TO PERMANENT BLINDESS
CONJUNCTIVITIS AND
CORNEAL ULCERATIONS
BLEEDING DIATHESIS (INCREASED TENDENCY
TO BLEED, SECONDARY TO MALABSORPTION
OF FAT-SOLUBLE VITAMIN K)
STANDARD ERROR OF THE MEAN (SEM) = Σ/√N
STEP 1
ORGAN SYSTEMS
IN UP TO ONE QUARTER OF CHILDREN
DIAGNOSED, RICKETS MAY BE A
PRESENTING SYMPTOM
CARDIOLOGY
LARGE VESSEL VASCULITIS
GIANT CELL (TEMPORAL) ARTERITIS
GRANULOMATOUS LARGE VESSEL
VASCULITIS INVOLVING SUPERFICIAL
TEMPORAL AND OPHTHALMIC ARTERIES
IT OCCURS MOST OFTEN IN ADULTS
OVER THE AGE OF 50
SYMPTOMS INCLUDE
TEMPORAL HEADACHE
JAW
CLAUDICATION
BLINDNESS IN THE IPSILATERAL EYE DUE TO
OPHTHALMIC ARTERY VASCULITIS
COMMONLY ASSOCIATED WITH POLYMYALGIA RHEUMATICA,
WHICH IS CHARACTERIZED BY MUSCLE AND JOINT PAIN, AND
NORMAL SERUM CREATINE KINASE
DIAGNOSIS
MADE BY BIOPSY, WHICH REVEALS
INFLAMED VESSEL WALL WITH GIANT CELLS
AND INTIMAL FIBROSIS
LESIONS ARE SEGMENTAL, REQUIRING BIOPSY
OF A LONG SEGMENT OF A VESSEL
A NEGATIVE RESULT DOES
NOT RULE OUT THE DISEASE
A COMMON LABORATORY FINDING
INCLUDES AN INCREASED ESR AND IS USED
AS A SCREENING TEST
TREATMENT
CORTICOSTEROIDS
TAKAYASU ARTERITIS
TAKAYASU ARTERITIS, ALSO KNOWN AS PULSELESS DISEASE,
IS A GRANULOMATOUS LARGE VESSEL VASCULITIS INVOLVING
AORTIC ARCH VESSELS
IT OCCURS MOST OFTEN IN YOUNG
ASIAN WOMEN AND CHILDREN
SYMPTOMS INCLUDE:
ABSENT UPPER EXTREMITY PULSE
DISCREPANCY IN BLOOD PRESSURE
BETWEEN THE ARMS (>10 MM HG)
NIGHT SWEATS
ARTHRITIS
MYALGIAS
SKIN NODULES
VISUAL DEFECTS
STROKE
TREATMENT
CORTICOSTEROIDS
PATHOLOGY
PHARMACOLOGY
ANTIHYPERTENSION DRUGS:
ANGIOTENSIN AGENTS
ACE INHIBITORS
“-PRIL”—EG, BENAZEPRIL, CAPTOPRIL, ENALAPRIL,
LISINOPRIL, RAMIPRIL
MECHANISM
INHIBITS THE CONVERSION OF ANGIOTENSIN I
TO ANGIOTENSIN II
NORMALLY, ACE BREAKS DOWN
BRADYKININ
ACE INHIBITORS WILL INCREASE
BRADYKININ LEVELS
SIDE EFFECTS
↓ ANGIOTENSIN II → ↓ ALDOSTERONE RELEASE → HYPERKALEMIA
↓ ANGIOTENSIN II → LESS CONSTRICTION OF EFFERENT
ARTERIOLES → ↓ GFR → UP TO 30% ↑ IN SERUM CR IS
EXPECTED IN MOST PATIENTS WITHIN 2-5 DAYS OF
INITIATING ACE INHIBITOR THERAPY
NOTE: ACE INHIBITORS CAN PRECIPITATE ACUTE RENAL FAILURE IN PATIENTS WHO
DEPEND ON EFFERENT ARTERIOLAR CONSTRICTION TO MAINTAIN GFR—EG,
HYPOVOLEMIA, DECOMPENSATED HEART FAILURE, RENAL ARTERY STENOSIS,
CHRONIC KIDNEY DISEASE.
TASTE DISTURBANCE (METALLIC TASTE)
RASH
IMPAIRED BRADYKININ METABOLISM BY ACE → ↑ BRADYKININ LEVELS → DRY COUGH, ANGIOEDEMA
CROSSES PLACENTA → FETOPATHIC
HEADACHE, FATIGUE, NAUSEA
FIRST DOSE ORTHOSTATIC HYPOTENSION
MNEMONIC
CAPTOPRIL’S CATCH
COUGH, ANGIOEDEMA, TERATOGEN,
INCREASED CREATININE, HYPERKALEMIA,
AND HYPOTENSION
ARBs (ANGIOTENSIN II
RECEPTOR BLOCKERS)
“-SARTAN”—EG, AZILSARTAN,
CANDESARTAN, EPROSARTAN, IRBESARTAN,
LOSARTAN, VALSARTAN
MECHANISM
BLOCK THE ACTIVATION OF
ANGIOTENSIN II RECEPTORS
NOT ASSOCIATED WITH A COUGH SIDE
EFFECT BECAUSE THEY DO NOT AFFECT
THE METABOLISM OF BRADYKININ BY ACE
IN CONTRAST, ACE INHIBITORS
PREVENT THE BREAKDOWN OF
BRADYKININ
→ THE RESULTING INCREASE IN BRADYKININ
HAS BEEN IMPLICATED AS THE CAUSE OF
ACE INHIBITOR-INDUCED COUGH
SIDE EFFECTS
HYPERKALEMIA
CROSSES PLACENTA, TERATOGENIC
ENDOCRINOLOGY
HYPOTHALAMIC-PITUITARY AXIS
ANTERIOR PITUITARY
THE ANTERIOR PITUITARY
(ADENOHYPOPHYSIS), AND
THE HORMONE-SECRETING
CELLS IT CONTAINS, ARE
DERIVED EMBRYOLOGICALLY
FROM SURFACE ECTODERM
(RATHKE’S POUCH)
THERE ARE SEVEN MAJOR
HORMONES SECRETED BY
THE ANTERIOR PITUITARY
TO REMEMBER THESE
HORMONES, USE THE
MNEMONIC "MY FLAT PIG"
MELANOCYTE-STIMULATING
HORMONE (MSH, OR
MELANOTROPIN) STIMULATES
MELANIN SYNTHESIS
IT IS DERIVED FROM
PRO-OPIOMELANOCORTIN, A
PRECURSOR IT SHARES WITH
ACTH
FOLLICLE STIMULATING
HORMONE (FSH) SIMULATES
GROWTH OF OVARIAN
FOLLICULES AND ESTROGEN
SECRETION IN FEMALES, AND
PROMOTES SPERM
MATURATION IN THE TESTES
LUTEINIZING HORMONE (LH)
STIMULATE
STEROIDOGENESIS IN THE
OVARY AND TESTES
IT ALSO STIMULATES
OVULATION AND CORPUS
LUTEUM FORMATION IN
FEMALES
ADRENOCORTICOTROPIC HORMONE (ACTH)
STIMULATES ADRENAL GROWTH AND
STEROIDOGENESIS
THYROID STIMULATING
HORMONE (TSH;
THYROTROPIN) STIMULATES
THYROID HORMONE
SYNTHESIS AND RELEASE
PROLACTIN STIMULATES MILK
PRODUCTION AND BREAST
DEVELOPMENT
GROWTH HORMONE (GH,
SOMATOTROPIN) IS
COUNTER-REGULATORY TO
INSULIN
IT STIMULATES SOMATIC
GROWTH VIA INSULIN-LIKE
GROWTH FACTOR (IGF-1),
WHICH IS RELEASED BY THE
LIVER IN RESPONSE TO
STIMULATION BY GH
TSH, LH AND FSH SHARE A
COMMON Α-SUBUNIT, WHILE
THE Β-SUBUNIT OF THESE
HORMONES DETERMINES
HORMONE SPECIFICITY
CELLS OF THE ANTERIOR
PITUITARY ARE CATEGORIZED
INTO TWO GROUPS,
BASOPHILS AND ACIDOPHILS,
BASED ON WHETHER THEY
STAIN READILY WITH ACIDIC
OR BASIC DYES
TO REMEMBER WHICH TYPE
OF HORMONE-SECRETING
CELLS FALL INTO WHICH
CATEGORY, USE THE
MNEMONICS “GPA” AND “B
FLAT”:
“GPA”: GH, PROLACTIN —
ACIDOPHILS
“B FLAT”: BASOPHILS — FSH,
LH, ACTH, TSH
ANTERIOR PITUITARY
HORMONES ENTER THE
SYSTEMIC CIRCULATION AND
EXERT THEIR EFFECTS AT
TARGET GLANDS
EVENTUALLY, THE TARGET
GLAND RESPONSE IS LIMITED
BY ITS HORMONAL PRODUCT
EXERTING NEGATIVE
FEEDBACK INHIBITION AT THE
LEVEL OF THE PITUITARY
GLAND OR HYPOTHALAMUS
A PROLACTINOMA IS THE
MOST COMMON PITUITARY
ADENOMA, WHICH
OVERPRODUCES THE
HORMONE PROLACTIN
SIGNS AND SYMPTOMS OF
PROLACTINOMA INCLUDE:
IMPOTENCE,
AMENORRHEA,
GYNECOMASTIA,
GALACTORRHEA, AND
HEADACHE
ENLARGEMENT OF THE
PITUITARY GLAND MAY ALSO
LEAD TO COMPRESSION OF
THE OPTIC CHIASM
THIS RESULTS IN A LOSS OF
PERIPHERAL VISION KNOWN
AS BITEMPORAL
HEMIANOPSIA
A PROLACTINOMA MAY HAVE
A MASS EFFECT ON THE
SURROUNDING PITUITARY
GLAND, CAUSING GENERAL
HYPOPITUITARY SYMPTOMS
PROLACTIN INCREASES DOPAMINE
SECRETION FROM
HYPOTHALAMUS
SUBSEQUENTLY, DOPAMINE
INHIBITS FURTHER PROLACTIN
SECRETION
PROLACTIN ALSO INHIBITS GNRH
BECAUSE OF THE
PHYSIOLOGICAL ACTION OF
DOPAMINE (SUPPRESSING
PROLACTIN), DOPAMINE
ANTAGONISTS (IE,
ANTIPSYCHOTICS) CAN
CAUSE GALACTORRHEA
FROM THIS LOSS OF
INHIBITION
THE TREATMENT FOR
PROLACTINOMA INCLUDES
BROMOCRIPTINE OR
CABERGOLINE, BOTH OF
WHICH ARE DOPAMINE
AGONISTS
DOPAMINE NORMALLY
INHIBITS PROLACTIN RELEASE
BROMOCRIPTINE CAN ALSO BE USED IN
THE TREATMENT OF PARKINSON’S
DISEASE
TRANSSPHENOIDAL SURGICAL
RESECTION MAY BE
INDICATED FOR LARGE
TUMORS
ANOTHER TYPE OF PITUITARY
ADENOMA IS ONE WHICH
INAPPROPRIATELY SECRETES
GH, LEADING TO
ACROMEGALY OR GIGANTISM
IF THE EXCESSIVE GH
SECRETION OCCURS DURING
CHILDHOOD, PRIOR TO
SKELETAL EPIPHYSEAL
CLOSURE, THE DISEASE STATE
THAT RESULTS IS GIGANTISM
IF THE EXCESSIVE GH
SECRETION OCCURS DURING
ADULTHOOD, AFTER
EPIPHYSEAL CLOSURE, THE
DISEASE STATE THAT RESULTS
IS ACROMEGALY
​GIGANTISM IS CHARACTERIZED BY DISPROPORTIONATELY LONG
LIMBS (INCREASED LINEAR BONE GROWTH), WHEREAS
ACROMEGALY PRESENTS AS CONSPICUOUS GROWTH IN THE SKIN
AND SOFT TISSUES, VISCERA, AND BONES OF THE FACE, HANDS,
AND FEET
SIGNS AND SYMPTOMS OF
ACROMEGALY INCLUDE:
COARSENING OF SKIN/FACIAL
FEATURES,
THICKENING OF THE HANDS
AND FEET,
ENLARGEMENT OF THE JAW
RESULTING IN PROTRUSION
(PROGNATHISM),
DEEP VOICE,
IMPAIRED GLUCOSE
TOLERANCE (INSULIN
RESISTANCE) AND
PERIPHERAL NEUROPATHIES
(DUE TO NERVE
COMPRESSION)
DIAGNOSIS IS MADE BASED
ON INCREASED INSULIN-LIKE
GROWTH FACTOR AND
MRI/CT IMAGING OF A
PITUITARY NEOPLASM
A GROWTH HORMONE
SUPPRESSION TEST MAY BE
PERFORMED TO DETERMINE
WHETHER GH PRODUCTION IS
SUPPRESSED BY HIGH BLOOD
SUGAR (INDUCED BY
DRINKING A GLUCOSE
SOLUTION)
THERE ARE THREE
TREATMENT OPTIONS FOR
GIGANTISM AND
ACROMEGALY:
SURGERY OR RADIATION
OCTREOTIDE, A
SOMATOSTATIN ANALOGUE
THAT INHIBITS GH RELEASE
FROM THE ANTERIOR
PITUITARY AND
PEGVISOMANT, A GH
RECEPTOR ANTAGONIST
WHICH EFFECTIVELY BLOCKS
IGF-1 PRODUCTION
HYPOPITUITARISM DESCRIBES
THE INSUFFICIENT SECRETION
OF PITUITARY HORMONES
RESULTING FROM DISEASES
OF THE HYPOTHALAMUS OR
THE PITUITARY
THE MAJORITY OF CASES OF
HYPOPITUITARISM ARE
SECONDARY TO DESTRUCTIVE
PROCESSES DIRECTLY
INVOLVING THE ANTERIOR
PITUITARY. THIS INCLUDES:
NONFUNCTIONAL PITUITARY
ADENOMAS (EXERTS
PRESSURE ON ADJACENT
PITUITARY CELLS)
PITUITARY SURGERY OR
RADIATION
TRAUMATIC BRAIN INJURY
AND SUBARACHNOID
HEMORRHAGE
PITUITARY APOPLEXY
(SUDDEN HEMORRHAGE INTO
THE PITUITARY GLAND)
SHEEHAN SYNDROME
(POSTPARTUM NECROSIS OF
THE ANTERIOR PITUITARY
SECONDARY TO INFARCTION
PRECIPITATED BY OBSTETRIC
HEMORRHAGE OR SHOCK)
EMPTY SELLA SYNDROME
(PRESENCE OF AN
ENLARGED, EMPTY SELLA
TURCICA DUE TO A
CONDITION THAT PARTIALLY
OR TOTALLY DESTROYS THE
PITUITARY GLAND;
CLASSICALLY AFFECTS OBESE
WOMEN WITH A HISTORY OF
MULTIPLE PREGNANCIES)
THE CLINICAL
MANIFESTATION OF
HYPOPITUITARISM DEPENDS
ON THE SPECIFIC
HORMONE(S) THAT ARE
LACKING
FOR EXAMPLE, A DEFICIENCY
OF MSH (SYNTHESIZED FROM
A COMMON PRECURSOR
WITH ACTH) CAN MANIFEST
AS PALLOR, DUE TO MSH'S
STIMULATORY EFFECTS ON
MELANOCYTES
THE TREATMENT FOR
HYPOPITUITARISM INCLUDES
HORMONE REPLACEMENT
THERAPY, INCLUDING:
CORTICOSTEROIDS,
T4 (THYROXINE),
SEX STEROIDS, AND
HUMAN GROWTH HORMONE
ENDOCRINE PANCREAS
DIABETES MELLITUS
DIABETES MELLITUS (DM) IS A METABOLIC DISEASE THAT IS CHARACTERIZED
BY A DEFICIENT OR INSUFFICIENT LEVEL OF INSULIN TO REGULATE BLOOD
GLUCOSE, RESULTING IN HYPERGLYCEMIA. THERE ARE TWO TYPES OF DM,
TYPE I AND TYPE II, WHICH DIFFER IN THEIR ETIOLOGY, COMPLICATIONS
AND TREATMENTS
HYPERGLYCEMIA RESULTS IN A CLASSIC TRIAD OF
SYMPTOMS SEEN IN DIABETIC PATIENTS, THE 3 PS-
POLYDIPSIA, POLYURIA AND POLYPHAGIA. UNINTENTIONAL
WEIGHT LOSS TYPICALLY ACCOMPANIES THESE SYMPTOMS
THERE ARE FOUR MAJOR METABOLIC
EFFECTS OF INSULIN DEFICIENCY AND/OR
END-ORGAN RESISTANCE TO INSULIN. THESE
INCLUDE
HEPATIC GLUCOSE OUTPUT
1. HEPATIC GLUCONEOGENESIS AND HEPATIC GLYCOGENOLYSIS
INCREASE, INCREASING THE AMOUNT OF GLUCOSE RELEASED FROM THE
LIVER. HEPATIC OUTPOURING OF GLUCOSE, WHEN COMBINED WITH THE
EFFECT OF DECREASED GLUCOSE UPTAKE BY MUSCLE AND ADIPOSE
TISSUE (DUE TO INSULIN DEFICIENCY AND/OR END-ORGAN RESISTANCE),
RESULTS IN:
HYPERGLYCEMIA, WHICH RESULTS IN GLUCOSURIA,
OSMOTIC DIURESIS, AND NONENZYMATIC
GLYCOSYLATION AFFECTING BLOOD VESSELS,
AND
NODULAR GLOMERULOSCLEROSIS (KIMMELSTIEL-WILSON
DISEASE), WHERE DENSE AREAS OF SCLEROSIS WITHIN THE
MESANGIUM FORM KIMMELSTIEL-WILSON NODULES
(PAS-POSITIVE, SPHERICAL NODULES LOCATED AT THE PERIPHERY
OF THE GLOMERULUS)
PROTEIN METABOLISM
2. THE NEED FOR ALTERNATIVE CELLULAR ENERGY LEADS TO AN INCREASE
IN PROTEIN CATABOLISM AND AN INCREASE IN AMINO ACID
PRODUCTION. ENERGY IS PRODUCED VIA AN INCREASE IN
GLUCONEOGENESIS FROM PROTEINS, AS WELL AS INCREASED MUSCLE
WASTING AND NITROGEN LOSS
FAT METABOLISM
3. ADIPOSE TISSUE IS BROKEN DOWN THROUGH INCREASED LIPOLYSIS,
RESULTING IN AN INCREASED RELEASE OF FREE FATTY ACIDS (FFAS) INTO
THE BLOOD STREAM. Β-OXIDATION OF THESE FFAS INCREASES
ACETYL-COA IN LIVER, WHICH SUBSEQUENTLY INCREASES HEPATIC
KETOGENESIS. CONSISTENTLY ELEVATED RATES OF KETOGENESIS IN THE
LIVER LEADS TO:
KETOACIDOSIS, MARKED BY THE ACCUMULATION OF
Β-HYDROXYBUTYRATE, ACETOACETATE AND ACETONE
(RESPONSIBLE FOR THE CHARACTERISTIC 'FRUITY BREATH'
OF DIABETICS),
INCREASED ANION GAP IN METABOLIC
ACIDOSIS (FROM ACCUMULATED KETONES),
AND
KETONURIA
PERIPHERAL LIPOPROTEIN
METABOLISM
4. A DECREASE OF CAPILLARY LIPOPROTEIN LIPASE ACTIVITY IN
PERIPHERAL BLOOD, WHICH RESULTS IN DECREASED BREAKDOWN OF
CHYLOMICRONS AND VLDL. THEREFORE, THE LEVELS OF
CHYLOMICRONS AND VLDL IN THE BLOOD INCREASE, CAUSING
HYPERTRIGLYCERIDEMIA
NONENZYMATIC GLYCOSYLATION (GLYCATION) IS A COMPLICATION OF
HYPERGLYCEMIA IN DIABETES WHICH LEADS TO ACCELERATED PRODUCTION OF
ADVANCED GLYCOSYLATION END PRODUCTS (AGES). AGES ARE FORMED THROUGH A
NONENZYMATIC REACTION BETWEEN INTRACELLULAR GLUCOSE-DERIVED
MOLECULES AND AN AMINO GROUP ON AN INTRACELLULAR OR EXTRACELLULAR
PROTEIN
THE DETRIMENTAL EFFECTS
OF AGES INCLUDE:
ƒƒDIFFUSE THICKENING OF BASEMENT
MEMBRANE, OR SMALL VESSEL DISEASE, WHICH
LEADS TO RETINOPATHY, GLAUCOMA, AND
NEPHROPATHY,
LARGE VESSEL ATHEROSCLEROSIS, CORONARY ARTERY
DISEASE, AND PERIPHERAL VASCULAR OCCLUSIVE DISEASE,
WHICH CAN LEAD TO CEREBROVASCULAR DISEASE AND MI
(MOST COMMON CAUSE OF DEATH), AND
GANGRENE, WHICH CAN
LEAD TO LIMB LOSS
HYPERGLYCEMIA THAT RESULTS FROM DECREASED GLUCOSE UPTAKE BY
INSULIN-DEPENDENT TISSUES LEADS TO INCREASED GLUCOSE UPTAKE BY
INSULIN-INDEPENDENT TISSUES. ALDOSE REDUCTASE IN INSULIN-INDEPENDENT CELLS
CONVERTS THIS EXCESS INTRACELLULAR GLUCOSE INTO SORBITOL, WHICH IS
OSMOTICALLY ACTIVE. THE EXCESS SORBITOL DRAWS WATER IN, CAUSING DAMAGE,
ESPECIALLY IN THE EYES AND NERVES
DIABETIC RETINOPATHY CAN RESULT FROM OSMOTIC DAMAGE TO PERICYTES.
SUBSEQUENT MICROANEURYSMS MAY OCCUR IN RETINAL VESSEL,
EVENTUALLY LEADING TO RETINAL MICROHEMORRHAGES, RETINAL EXUDATES
AND MACULAR EDEMA. OSMOTIC DAMAGE TO THE LENS INCREASES THE
RISK OF CATARACTS. DIABETICS ARE ALSO AT A HIGHER RISK FOR
GLAUCOMA
DIABETIC NEUROPATHY IS THE RESULT OF OSMOTIC DAMAGE TO SCHWANN CELLS,
WHICH CAN LEAD TO DEMYELINATION AND SENSORIMOTOR PERIPHERAL NEUROPATHY.
THE PERIPHERAL NEUROPATHY IS MOST COMMONLY A “STOCKING-GLOVE” DISTAL
SYMMETRIC POLYNEUROPATHY. THIS LOSS OF SENSATION IN THE DISTAL EXTREMITIES
CAN LEAD TO NEUROPATHIC PRESSURE ULCERS, MOST COMMONLY IN THE FEET
(DIABETIC FOOT ULCERS)
AUTONOMIC NERVES MAY ALSO BE DAMAGED, LEADING
TO AUTONOMIC NEUROPATHY THAT MANIFESTS AS
BLADDER AND/OR BOWEL INCONTINENCE AND
IMPOTENCE
HYPOGLYCEMIA MAY RESULT IN DIABETIC
PATIENTS USING INSULIN, IF IT IS NOT
ADMINISTERED APPROPRIATELY
SYMPTOMS GENERALLY
APPEAR AT GLUCOSE < 70
MG/DL
THE SYMPTOMS OF HYPOGLYCEMIA CAN
REMEMBERED WITH THE MNEMONIC STAB
AT DIABETES:
SWEATING
TREMOR
ANXIETY OR AGITATION
BLURRY VISION
ALTERED MENTAL STATUS
TACHYCARDIA
SEVERAL LAB TESTS CAN AID IN THE DIAGNOSIS OF DM.
THESE INCLUDE FASTING GLUCOSE LEVELS, AN ORAL
GLUCOSE TOLERANCE TEST, AND HEMOGLOBIN A1C
LEVELS
1) A FASTING SERUM GLUCOSE LEVEL ≥ 126 MG/DL (7.0
MMOL/L) THAT IS MEASURED ON TWO SEPARATE
OCCASIONS, IS DIAGNOSTIC FOR DM. FASTING IS DEFINED
AS 8 HOURS WITHOUT CALORIC INTAKE
2) AN ORAL GLUCOSE TOLERANCE TEST MEASURES
POSTPRANDIAL PLASMA GLUCOSE LEVELS, 2 HOURS
FOLLOWING A 75-GRAM GLUCOSE BOLUS. PLASMA
GLUCOSE LEVELS ≥ 200 MG/DL (11.1 MMOL/L) ARE
DIAGNOSTIC FOR DM
3) HEMOGLOBIN A1C (HBA1C) IS A MEASURE OF NON-ENZYMATIC
GLYCATION THAT OCCURS ON THE BETA CHAIN OF THE HEMOGLOBIN
MOLECULE UPON EXPOSURE TO GLUCOSE IN THE PLASMA. HBA1C ≥ 6.5%
IS PART OF THE DIAGNOSTIC CRITERIA FOR DM. THE GOAL FOR LONG
TERM MANAGEMENT OF DIABETES IS TO MAINTAIN HBA1C LEVELS
BETWEEN 6-7%
IN ADDITION TO THE ABOVE TESTS, IF A RANDOM PLASMA
GLUCOSE (RPG) TEST MEASURES 200 MG/DL OR HIGHER, AND
THE PATIENT IS SHOWING SYMPTOMS OF DIABETES
(POLYPHAGIA, POLYDIPSIA, POLYURIA), DIABETES MAY BE
DIAGNOSED
TYPE I DIABETES MELLITUS
TYPE 1 DIABETES MELLITUS (T1DM) IS CAUSED BY AN
AUTOINFLAMMATORY OR VIRAL DESTRUCTION OF THE BETA
CELLS OF THE ENDOCRINE PANCREAS, WHICH SYNTHESIZE
INSULIN. DESTRUCTION RESULTS IN INSULIN DEFICIENCY
T1DM TYPICALLY HAS AN ONSET IN
CHILDHOOD OR ADOLESCENCE, COMPARED TO
T2DM WHICH COMMONLY PRESENTS IN
ADULTHOOD
INSULIN IS THE ESSENTIAL TREATMENT; ORAL
HYPOGLYCEMICS WILL NOT WORK SINCE
THEY REQUIRE FUNCTIONAL BETA ISLET
CELLS
GENETIC PREDISPOSITION FOR T1DM IS
WEAK, HOWEVER THERE IS AN
ASSOCIATION WITH HLA-DR3 AND 4
HISTOLOGICALLY, AN ISLET LEUKOCYTE
INFILTRATE IS SEEN IN T1DM (BUT NOT IN
T2DM)
SINCE T1DM RESULTS FROM AN ABSOLUTE DEFICIENCY OF
INSULIN PRODUCTION FROM BETA ISLET CELLS, THE CLASSIC
DRUGS USED IN T2DM CAN'T BE USED. INSTEAD, T1DM IS
MANAGED THROUGH ADMINISTRATION OF DIFFERENT FORMS OF
INSULIN
INSULIN MEDICATIONS VARY ACCORDING TO THEIR DURATION OF ACTION. IN A PATIENT
WITH A NORMAL PANCREAS, THERE IS A BASAL LEVEL OF INSULIN THAT CONTROLS
FASTING BLOOD SUGAR, WITH SURGES OF INSULIN AFTER MEALS TO PREVENT
POST-PRANDIAL HYPERGLYCEMIA. IN PATIENTS WITH T1DM, A COMBINATION OF
LONG-ACTING (BASAL) INSULIN AND SHORTER-ACTING (POST-PRANDIAL) INSULIN IS USED
TO MIMIC NORMAL PHYSIOLOGY
SINCE INSULIN IS A PEPTIDE, IT WOULD BE DEGRADED IN THE GI TRACT IF
TAKEN ORALLY. THEREFORE, ROUTINE SUBCUTANEOUS ADMINISTRATION BY A
PUMP, NEEDLE, OR PEN IS RECOMMENDED (INTRAMUSCULAR INJECTION
CARRIES HIGHER RISK). NOTE THAT INSULIN MAY BE GIVEN IV IN A HOSPITAL
SETTING IF THE PATIENT IS EXPERIENCING A DIABETIC EMERGENCY (EG, DKA OR
HHNK)
GLUCOSE LEVELS MUST BE CHECKED
FREQUENTLY TO AVOID HYPOGLYCEMIA, THE
MOST COMMON COMPLICATION OF T1DM
INSULIN-INDUCED HYPOGLYCEMIA CAN BE
TREATED WITH ORAL SUGAR, OR
INTRAMUSCULAR GLUCAGON
RAPID-ACTING INSULINS HAVE A RAPID ONSET AND AN
EARLY PEAK OF ACTIVITY, PERMITTING CONTROL OF
POSTPRANDIAL GLUCOSE. EXAMPLES OF RAPID-ACTING
INSULINS INCLUDE:
INSULIN LISPRO
INSULIN ASPART
INSULIN GLULISINE
TO REMEMBER THE RAPID-ACTING INSULINS,
USE THE MNEMONIC, "THERE'S NO LAG
WITH RAPID-ACTING INSULINS"
THE ONSET OF RAPID-ACTING INSULIN IS 15 MINUTES.
ITS PEAK EFFECT IS 30-90 MINUTES AFTER
ADMINISTRATION, AND ITS DURATION IS BETWEEN 3-5
HOURS
SHORT-ACTING INSULIN IS THE SAME AS THE NORMAL
INSULIN SECRETED IN OUR BODIES. SHORT-ACTING INSULIN
IS DIFFERENT FROM RAPID-ACTING INSULIN, SUCH AS
GLULISINE, LISPRO AND ASPART
SHORT-ACTING INSULIN HAS AN ONSET OF 30 AND 60
MINUTES. ITS PEAK EFFECT IS 2-4 HOURS AFTER
ADMINISTRATION, AND IT HAS A DURATION OF 5-8
HOURS
AN EXAMPLE OF INTERMEDIATE-ACTING INSULIN IS
ISOPHANE (NPH). NPH IS OFTEN COMBINED WITH
RAPID-ACTING AND SHORT-ACTING (REGULAR)
INSULIN
NPH HAS AN ONSET OF 1-3 HOURS, AND A
PEAK EFFECT AT 8 HOURS.
INTERMEDIATE-ACTING INSULIN HAS A
DURATION OF 12-16 HOURS
LONG-ACTING INSULINS INCLUDE INSULIN GLARGINE AND INSULIN
DETEMIR. THESE INSULINS ARE USED TO HELP CONTROL BASAL LEVELS OF
GLUCOSE. IN OTHER WORDS, LONG-ACTING INSULINS ENSURE A SMALL
AMOUNT OF INSULIN IS IN THE BLOOD STREAM TO ASSIST IN THE
MOVEMENT OF GLUCOSE INTO CELLS AROUND THE CLOCK
LONG-ACTING INSULINS ALL HAVE AN ONSET OF 1 HOUR,
AND A DURATION OF 20-26 HOURS (GLARGINE HAS A
LONGER DURATION THAN DETEMIR). NOTE THAT
LONG-ACTING INSULINS ARE "PEAKLESS"
DIABETIC KETOACIDOSIS (DKA) IS AN IMPORTANT COMPLICATION OF T1DM.
NOTE THAT DKA CAN ALSO OCCUR IN T2DM, HOWEVER HYPEROSMOLAR
HYPERGLYCEMIC NONKETOTIC ACIDOSIS IS A MORE COMMON
COMPLICATION IN THESE PATIENTS. DKA IS OFTEN PRECIPITATED BY
INCREASED STRESS, INFECTION, OR NONCOMPLIANCE WITH
MEDICATIONS/DIET, OR TRAUMA
IN A DIABETIC PATIENT, A COMPLETE LACK OF INSULIN PRODUCTION, OR A
RELATIVE INSULIN DEFICIENCY LEADS TO THE USE OF FATS AS A
SIGNIFICANT ENERGY SOURCE. KETOSIS IS AN INCREASE IN FATTY ACID
METABOLISM TO PRODUCE KETONE BODIES, NAMELY
Β-HYDROXYBUTYRATE AND ACETOACETATE, AS AN ALTERNATIVE FUEL
SOURCE
IN DKA, HYPERGLYCEMIA INDUCES PROFOUND OSMOTIC DIURESIS, WHICH
CAUSES WATER AND ELECTROLYTE LOSS (ESPECIALLY POTASSIUM). METABOLIC
ACIDOSIS FORCES HYDROGEN IONS INTO CELLS, WHICH DISPLACES K+ IONS
THAT ARE SUBSEQUENTLY LOST IN THE URINE. THE MNEMONIC "REMEMBER THE
3 K'S, OR LOSE AOA" CAN BE USED TO REMEMBER THE CLINICAL HALLMARKS OF
DKA:
KUSSMAUL RESPIRATIONS
(RAPID, DEEP BREATHING),
ELEVATED KETONES IN THE
URINE AND BLOOD,
[K+] ELEVATED IN THE SERUM
DUE TO ELECTROLYTE SHIFT,
ALTHOUGH TOTAL BODY [K+]
IS DEPLETED
SEVERE WATER LOSS,
LEADING TO DEHYDRATION
AND HYPOTENSION,
POSITIVE ANION GAP,
"FRUITY" ODOR ON BREATH,
AND
ABDOMINAL PAIN
SEVERE COMPLICATIONS OF DKA INCLUDE HEART
FAILURE AND/OR ARRHYTHMIAS, CEREBRAL EDEMA,
AND MUCOR SINUSITIS (A FATAL FUNGAL
INFECTION)
THE TREATMENT OF DKA INCLUDES NORMAL SALINE FLUID
RESUSCITATION IN ORDER TO CORRECT FLUID DEFICIT (REHYDRATION)
AND REDUCE PLASMA OSMOLARITY. POTASSIUM AND INSULIN ARE GIVEN
ALONG WITH GLUCOSE (TO PREVENT THE PATIENT FROM BECOMING
HYPOGLYCEMIC)
TYPE II DIABETES MELLITUS
IN TYPE 2 DIABETES MELLITUS
(T2DM), PANCREATIC BETA
CELL PRODUCTION OF
INSULIN IS INITIALLY NORMAL,
BUT BECOMES INSUFFICIENT
DUE TO PERIPHERAL INSULIN
RESISTANCE, IMPAIRED
GLUCOSE TOLERANCE, AND
COMPLETE OR PARTIAL BETA
CELL DYSFUNCTION
THE ONSET OF T2DM
USUALLY OCCURS IN ADULTS,
AND OFTEN WITH A STRONG
FAMILY HISTORY AND
ASSOCIATION WITH MORBID
OBESITY. UNLIKE T1DM,
THERE IS NO ASSOCIATION
WITH T2DM AND THE HLA
SYSTEM
T2DM IS CAUSED BY A
COMBINATION OF GENETIC
AND ENVIRONMENTAL
FACTORS, AND HAS BEEN
ASSOCIATED WITH POOR
DIET, LACK OF EXERCISE, AND
OBESITY
SINCE SOME AMOUNT OF INSULIN IS AVAILABLE IN T2DM, KETOACIDOSIS IS UNLIKELY TO
OCCUR —TRUE DKA IS AN UNCOMMON (BUT NOT IMPOSSIBLE) COMPLICATION OF
UNCONTROLLED T2DM. HOWEVER, UNCONTROLLED TYPE 2 DIABETICS ARE AT RISK OF
DEVELOPING HYPEROSMOLAR HYPERGLYCEMIC NONKETOTIC SYNDROME, A CONDITIONS
WHICH RESULTS IN HYPEROSMOLAR INTRAVASCULAR DEHYDRATION THAT, IF LEFT
UNTREATED, CAN PROGRESS TO HYPERGLYCEMIC DIABETIC COMA
THE MOST COMMON
SYMPTOMS OF
HYPERGLYCEMIA INCLUDE
POLYDIPSIA AND POLYURIA
HISTOLOGICALLY, ISLET
AMYLOID POLYPEPTIDE
DEPOSITS ARE SEEN IN T2DM
(BUT NOT IN T1DM)
THERE ARE EIGHT MAJOR CLASSES OF ORAL
ANTIDIABETIC AGENTS, WHICH CAN BE REMEMBERED
WITH THE MNEMONIC STΑB MELLITUS WITH A
DAGGER:
SULFONYLUREAS
THIAZOLIDINEDIONES
Α-GLUCOSIDASE INHIBITORS
BIGUANIDES
MEGLITINIDES
DIPEPTIDYL PEPTIDASE-4
INHIBITORS
AMYLIN ANALOGUES
GLUCAGON-LIKE
POLYPEPTIDE-1 ANALOGS
THE LAST THREE CLASSES LISTED (DAG)
ARE NEWER CLASSES OF DIABETES
MEDICATION
SULFONYLUREAS (CHLORPROPAMIDE, TOLBUTAMIDE,
GLYBURIDE, GLIPIZIDE) INCREASE INSULIN SECRETION BY
CLOSURE OF ATP-GATED K+ CHANNEL IN THE PANCREATIC
Β-CELL MEMBRANE
REMEMBER THAT GLUT-2
TRANSPORTERS BRING
GLUCOSE INTO PANCREATIC
Β-CELLS, WHERE IT IS
METABOLIZED TO PRODUCE
ATP VIA AEROBIC
RESPIRATION. THE RISE IN ATP
CLOSES ATP-GATED K+
CHANNELS. WHEN K+
CHANNELS ARE CLOSED, THE
CELL DEPOLARIZES CAUSING
VOLTAGE-GATED CA2+
CHANNELS TO OPEN. THIS
RELEASE OF CA2+ TRIGGERS
THE RELEASE OF INSULIN
THERE ARE TWO GENERATIONS OF SULFONYLUREAS. FIRST GENERATION
SULFONYLUREAS HAVE LONGER HALF-LIVES AND INCLUDE CHLORPROPAMIDE AND
TOLBUTAMIDE. SECOND GENERATION SULFONYLUREAS ARE MORE POTENT AND HAVE
SHORTER HALF-LIVES. THEY INCLUDE GLYBURIDE (THE DOSE OF WHICH MUST BE
DECREASED WITH RENAL FAILURE) AND GLIPIZIDE (THE DOSE OF WHICH MUST BE
DECREASED WITH LIVER FAILURE)
​OVERADMINISTRATION OF
SULFONYLUREAS CAN LEAD TO
HYPOGLYCEMIA
THIAZOLIDINEDIONES
(ROSIGLITAZONE,
PIOGLITAZONE) IMPROVE
INSULIN TARGET SENSITIVITY.
THEY BIND TO PPAR-Γ
(PEROXISOME PROLIFERATOR
ACTIVATING
RECEPTOR-GAMMA), CAUSING
INCREASED INSULIN
RECEPTOR NUMBER AND
SENSITIVITY, AS WELL AS
DECREASED HEPATIC
GLUCONEOGENESIS
SIDE EFFECTS OF THIAZOLIDINEDIONES INCLUDE
HEPATOTOXICITY AND CARDIOVASCULAR TOXICITY, WITH
ABSOLUTE CONTRAINDICATION IN PATIENTS WITH LIVER
FAILURE OR CHF
COMMONLY USED THIAZOLIDINEDIONE
MEDICATIONS INCLUDE ROSIGLITAZONE
AND PIOGLITAZONE
Α-GLUCOSIDASE INHIBITORS (ACARBOSE, MIGLITOL)
PREVENT DISACCHARIDES IN THE GUT FROM THEIR FINAL
DEGRADATION INTO MONOSACCHARIDES BY BRUSH
BORDER ENZYMES, PRIOR TO ABSORPTION
THIS CLASS OF DRUGS IS
POORLY TOLERATED BY
PATIENTS. IN EFFECT, THEY
ARE SIMULATING A
DISACCHARIDASE DEFICIENCY
(E.G. LACTOSE
INTOLERANCE), CAUSING
OSMOTIC DIARRHEA AND
PRESENTING MORE SUGARS
TO THE COLONIC FLORA.
THE COLONIC FLORA
DIGESTS THESE SUGARS,
RELEASING GAS AND
CAUSING FLATULENCE
TWO COMMONLY USED Α-GLUCOSIDASE
INHIBITORS ARE ACARBOSE AND
MIGLITOL
BIGUANIDES (METFORMIN) REPRESS HEPATIC GLUCONEOGENESIS AND INCREASE
PERIPHERAL INSULIN SENSITIVITY AND UTILIZATION OF GLUCOSE. (ALTHOUGH UNCLEAR, THE
PROPOSED MECHANISM OF BIGUANIDES (METFORMIN) IS THAT THEY ACTIVATE
AMP-ACTIVATED PROTEIN KINASE (AMPK), WHICH INCREASE EXPRESSION OF A SMALL
HETERODIMER PARTNER (SHP). SHP INHIBITS EXPRESSION OF LIVER PHOSPHOENOLPYRUVATE
CARBOXYKINASE (PEPCK) AND GLUCOSE-6-PHOSPHATASE, THUS REPRESSING HEPATIC
GLUCONEOGENESIS)
SIDE EFFECTS OF METFORMIN
INCLUDE:
GI DISTRESS (EG, DIARRHEA),
WEIGHT LOSS AND
LACTIC ACIDOSIS WHICH IS
RARE, BUT HAS A 50%
MORTALITY WHEN IT OCCURS. THIS IS MOST COMMONLY
SEEN IN PATIENTS WITH
UNDERLYING RENAL DISEASE
METFORMIN IS THE MOST
IMPORTANT EXAMPLE OF A
BIGUANIDE, AND IS THE FIRST
LINE AGENT FOR T2DM
MEGLITINIDES (REPAGLINIDE,
NATEGLINIDE) ARE
NON-SULFONYLUREA
SECRETAGOGUES (INCREASE
INSULIN SECRETION)
THE MAJOR SIDE EFFECT OF
MEGLITINIDES IS
HYPOGLYCEMIA (JUST LIKE
SULFONYLUREAS)
TWO IMPORTANT
MEGLITINIDES ARE
REPAGLINIDE AND
NATEGLINIDE
DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS (SITAGLIPTIN,
SAXAGLIPTIN, AND LINAGLIPTIN) INHIBIT THE DEGRADATION
OF INCRETIN AND THUS INCREASE CIRCULATING LEVELS OF
GLP-1 AND GLUCOSE-DEPENDENT INSULINOTROPIC
POLYPEPTIDE (GIP)
THESE MEDICATIONS HELP REGULATE
POST-PRANDIAL GLUCOSE FLUCTUATIONS
AND DECREASE GLUCAGON LEVELS
AMYLIN ANALOGUES
(PRAMLINTIDE) SUPPRESS
GLUCAGON RELEASE AND
HELP REGULATE
POSTPRANDIAL BLOOD
GLUCOSE.
DIABETES CAN CAUSE THE
SUPPRESSION OF
GLUCAGON-LIKE POLYPEPTIDE
1 (GLP-1) RELEASE, WHICH
RESULTS IN EXCESSIVE
HEPATIC GLUCOSE OUTPUT.
GLP-1 ANALOGS (EXENATIDE,
LIRAGLUTIDE) INCREASE
INSULIN AND DECREASE
GLUCAGON OUTPUT
OTHER THERAPIES FOR T2DM
TARGET RELATED
MORBIDITIES, AND INCLUDE
LIFESTYLE MODIFICATIONS,
ACE INHIBITORS AND
VACCINES
LIFESTYLE MODIFICATIONS
INCLUDE SMOKING
CESSATION, HEALTHY EATING
HABITS AND ADOPTING AN
ACTIVE LIFESTYLE
ACE INHIBITORS ARE USED
PROPHYLACTICALLY IN
PATIENTS WITH DIABETIC
NEPHROPATHY (REGARDLESS
OF BLOOD PRESSURE), DUE
TO THEIR ABILITY TO DILATE
THE NEPHRON’S EFFERENT
ARTERIOLES, WHICH
DECREASES FILTRATION
PRESSURE. THIS DECREASES
THE AMOUNT OF PROTEIN IN
THE URINE AND PREVENTS OR
SLOWS THE PROGRESSION
OF DIABETES-RELATED
KIDNEY DISEASE
BECAUSE OF THE
IMMUNOSUPPRESSIVE EFFECT
OF DIABETES, VACCINES
SUCH AS PNEUMOVAX AND
AN ANNUAL FLU SHOT
SHOULD BE ENCOURAGED IN
DIABETIC PATIENTS
GESTATIONAL DIABETES
MELLITUS IS DEFINED AS THE
PRESENCE OF GLUCOSE
INTOLERANCE
(HYPERGLYCEMIA) DURING
PREGNANCY, WHICH WAS
NOT PRESENT PRIOR TO
CONCEPTION. IT GENERALLY
APPEARS AROUND THE 24TH
WEEK OF PREGNANCY
50% OF CARRIERS OF THE
GLUCOKINASE GENE
MUTATION (WHICH
INCREASES THE GLUCOSE
THRESHOLD THAT TRIGGERS
INSULIN RELEASE) DEVELOP
GESTATIONAL DIABETES
MELLITUS.
DIETARY MODIFICATIONS
AND EXERCISE SHOULD BE
ENCOURAGED IN PATIENTS
WITH GESTATIONAL
DIABETES. IF LIFESTYLE
MODIFICATION EFFORTS FAIL,
INSULIN REPLACEMENT MAY
BE NECESSARY
ENDOCRINE PHARMACOLOGY
DIABETES MELLITUS
PHARMACOLOGY
THE ESSENTIAL TREATMENT
FOR TYPE 1 DIABETES
MELLITUS T1DM IS INSULIN
TYPE 2 DIABETES MELLITUS (T2DM) IS MANAGED
BY ORAL HYPOGLYCEMIC MEDICATIONS,
ALTHOUGH INSULIN MAY BE ADDED TO A
REGIMEN
INSULIN MEDICATIONS VARY
ACCORDING TO THEIR
DURATION OF ACTION
IN A PATIENT WITH A NORMAL PANCREAS, THERE IS A
BASAL LEVEL OF INSULIN THAT CONTROLS FASTING BLOOD
SUGAR, WITH SURGES OF INSULIN AFTER MEALS TO
PREVENT POST-PRANDIAL HYPERGLYCEMIA
IN PATIENTS WITH T1DM, A COMBINATION OF
LONG-ACTING (BASAL) INSULIN AND SHORTER-ACTING
(POST-PRANDIAL) INSULIN IS USED TO MIMIC NORMAL
PHYSIOLOGY
SINCE INSULIN IS A PEPTIDE, IT WOULD
BE DEGRADED IN THE GI TRACT IF
TAKEN ORALLY
THEREFORE, ROUTINE SUBCUTANEOUS
ADMINISTRATION BY A PUMP, NEEDLE, OR PEN IS
RECOMMENDED (INTRAMUSCULAR INJECTION CARRIES
HIGHER RISK)
NOTE THAT INSULIN MAY BE GIVEN IV IN A
HOSPITAL SETTING IF THE PATIENT IS
EXPERIENCING A DIABETIC EMERGENCY (EG, DKA
OR HHNK)
GLUCOSE LEVELS MUST BE CHECKED
FREQUENTLY TO AVOID HYPOGLYCEMIA, THE
MOST COMMON COMPLICATION OF T1DM
INSULIN-INDUCED
HYPOGLYCEMIA CAN BE
TREATED WITH ORAL SUGAR,
OR INTRAMUSCULAR
GLUCAGON
RAPID-ACTING INSULINS HAVE A RAPID ONSET AND AN
EARLY PEAK OF ACTIVITY, PERMITTING CONTROL OF
POSTPRANDIAL GLUCOSE. EXAMPLES OF RAPID-ACTING
INSULINS INCLUDE:
INSULIN LISPRO
INSULIN ASPART
INSULIN GLULISINE
TO REMEMBER THE RAPID-ACTING INSULINS,
USE THE MNEMONIC, "THERE'S NO LAG
WITH RAPID-ACTING INSULINS"
THE ONSET OF RAPID-ACTING
INSULIN IS 15 MINUTES
ITS PEAK EFFECT IS 30-90 MINUTES AFTER
ADMINISTRATION, AND ITS DURATION IS
BETWEEN 3-5 HOURS
SHORT-ACTING INSULIN IS THE SAME AS
THE NORMAL INSULIN SECRETED IN OUR
BODIES
SHORT-ACTING INSULIN IS DIFFERENT FROM
RAPID-ACTING INSULIN, SUCH AS
GLULISINE, LISPRO AND ASPART
SHORT-ACTING INSULIN HAS
AN ONSET OF 30 AND 60
MINUTES
ITS PEAK EFFECT IS 2-4 HOURS AFTER
ADMINISTRATION, AND IT HAS A DURATION
OF 5-8 HOURS
AN EXAMPLE OF
INTERMEDIATE-ACTING
INSULIN IS NPH
NPH IS OFTEN COMBINED WITH
RAPID-ACTING AND SHORT-ACTING
(REGULAR) INSULIN
NPH HAS AN ONSET OF 1-3
HOURS, AND A PEAK EFFECT
AT 8 HOURS
INTERMEDIATE-ACTING
INSULIN HAS A DURATION OF
12-16 HOURS
LONG-ACTING INSULINS
INCLUDE INSULIN GLARGINE
AND INSULIN DETEMIR
THESE INSULINS ARE USED TO HELP
CONTROL BASAL LEVELS OF
GLUCOSE
IN OTHER WORDS, LONG-ACTING INSULINS ENSURE A
SMALL AMOUNT OF INSULIN IS IN THE BLOOD STREAM TO
ASSIST IN THE MOVEMENT OF GLUCOSE INTO CELLS
AROUND THE CLOCK
LONG-ACTING INSULINS ALL HAVE AN ONSET OF 1
HOUR, AND A DURATION OF 20-26 HOURS
(GLARGINE HAS A LONGER DURATION THAN
DETEMIR)
NOTE THAT LONG-ACTING
INSULINS ARE "PEAKLESS"
THERE ARE NINE MAJOR CLASSES OF ORAL
ANTIDIABETIC AGENTS, WHICH CAN BE
REMEMBERED WITH THE MNEMONIC STΑB MELLITUS
WITH DAGS:
SULFONYLUREAS
SULFONYLUREAS (CHLORPROPAMIDE, TOLBUTAMIDE,
GLYBURIDE, GLIPIZIDE) INCREASE INSULIN SECRETION BY
CLOSURE OF ATP-GATED K+ CHANNEL IN THE PANCREATIC
Β-CELL MEMBRANE
REMEMBER THAT GLUT-2 TRANSPORTERS BRING
GLUCOSE INTO PANCREATIC Β-CELLS, WHERE IT IS
METABOLIZED TO PRODUCE ATP VIA AEROBIC
RESPIRATION
THE RISE IN ATP CLOSES
ATP-GATED K+ CHANNELS
WHEN K+ CHANNELS ARE CLOSED, THE
CELL DEPOLARIZES CAUSING
VOLTAGE-GATED CA2+ CHANNELS TO OPEN
THIS RELEASE OF CA2+
TRIGGERS THE RELEASE OF
INSULIN
THERE ARE TWO
GENERATIONS OF
SULFONYLUREAS
FIRST GENERATION SULFONYLUREAS HAVE
LONGER HALF-LIVES AND INCLUDE
CHLORPROPAMIDE AND TOLBUTAMIDE
SECOND GENERATION SULFONYLUREAS
ARE MORE POTENT AND HAVE SHORTER
HALF-LIVES
THEY INCLUDE GLYBURIDE (THE DOSE OF WHICH MUST BE
DECREASED WITH RENAL FAILURE) AND GLIPIZIDE (THE
DOSE OF WHICH MUST BE DECREASED WITH LIVER
FAILURE)
​OVERADMINISTRATION OF SULFONYLUREAS CAN LEAD TO
HYPOGLYCEMIA, THE RISK OF WHICH IS INCREASED IN
RENAL FAILURE ADDITIONALLY, FIRST GENERATION
SULFONYLUREAS CAN HAVE DISULFIRAM-LIKE EFFECTS
THIAZOLIDINEDIONES
THIAZOLIDINEDIONES (ROSIGLITAZONE,
PIOGLITAZONE) IMPROVE INSULIN TARGET
SENSITIVITY
THEY BIND TO PPAR-Γ (PEROXISOME PROLIFERATOR
ACTIVATING RECEPTOR-GAMMA), CAUSING INCREASED
INSULIN RECEPTOR NUMBER AND SENSITIVITY, AS WELL AS
DECREASED HEPATIC GLUCONEOGENESIS
SIDE EFFECTS OF THIAZOLIDINEDIONES INCLUDE
HEPATOTOXICITY AND CARDIOVASCULAR TOXICITY, WITH
ABSOLUTE CONTRAINDICATION IN PATIENTS WITH LIVER
FAILURE OR CHF
ADDITIONALLY, THEY CAN CAUSE WEIGHT
GAIN, EDEMA, AND INCREASED RISK OF
FRACTURES
COMMONLY USED THIAZOLIDINEDIONE
MEDICATIONS INCLUDE ROSIGLITAZONE
AND PIOGLITAZONE
Α-GLUCOSIDASE INHIBITORS
Α-GLUCOSIDASE INHIBITORS (ACARBOSE, MIGLITOL)
PREVENT DISACCHARIDES IN THE GUT FROM THEIR FINAL
DEGRADATION INTO MONOSACCHARIDES BY BRUSH
BORDER ENZYMES, PRIOR TO ABSORPTION
THIS CLASS OF DRUGS IS
POORLY TOLERATED BY
PATIENTS
IN EFFECT, THEY ARE SIMULATING A DISACCHARIDASE
DEFICIENCY (E.G. LACTOSE INTOLERANCE), CAUSING
OSMOTIC DIARRHEA AND PRESENTING MORE SUGARS TO
THE COLONIC FLORA
THE COLONIC FLORA DIGESTS THESE
SUGARS, RELEASING GAS AND CAUSING
FLATULENCE
TWO COMMONLY USED Α-GLUCOSIDASE
INHIBITORS ARE ACARBOSE AND
MIGLITOL
BIGUANIDES
BIGUANIDES (METFORMIN) REPRESS HEPATIC
GLUCONEOGENESIS AND INCREASE PERIPHERAL
INSULIN SENSITIVITY AND UTILIZATION OF
GLUCOSE
(ALTHOUGH UNCLEAR, THE PROPOSED MECHANISM OF
BIGUANIDES (METFORMIN) IS THAT THEY ACTIVATE
AMP-ACTIVATED PROTEIN KINASE (AMPK), WHICH INCREASE
EXPRESSION OF A SMALL HETERODIMER PARTNER (SHP)
SHP INHIBITS EXPRESSION OF LIVER
PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK) AND
GLUCOSE-6-PHOSPHATASE, THUS REPRESSING HEPATIC
GLUCONEOGENESIS)
SIDE EFFECTS OF METFORMIN
INCLUDE:
GI DISTRESS (E.G., DIARRHEA)
WEIGHT LOSS
LACTIC ACIDOSIS (RARE, BUT HAS A 50%
MORTALITY WHEN IT OCCURS; MOST COMMONLY
SEEN IN PATIENTS WITH UNDERLYING RENAL
DISEASE)
METFORMIN IS THE MOST IMPORTANT
EXAMPLE OF A BIGUANIDE, AND IS THE
FIRST LINE AGENT FOR T2DM
MEGLITINIDES
MEGLITINIDES (REPAGLINIDE, NATEGLINIDE)
INCREASE INSULIN SECRETION, AND THUS ARE
ALSO KNOWN AS NON-SULFONYLUREA
SECRETAGOGUES
THE MAJOR SIDE EFFECT OF MEGLITINIDES
IS HYPOGLYCEMIA (JUST LIKE
SULFONYLUREAS)
TWO IMPORTANT MEGLITINIDES
ARE REPAGLINIDE AND
NATEGLINIDE
DIPEPTIDYL PEPTIDASE-4
INHIBITORS
DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS
(SITAGLIPTIN, SAXAGLIPTIN, AND LINAGLIPTIN)
INHIBIT THE DEGRADATION OF INCRETINS BY
DPP-4
INCRETINS INCLUDE GLUCAGON-LIKE
PEPTIDE (GLP-1) AND GLUCOSE-DEPENDENT
INSULINOTROPIC POLYPEPTIDE (GIP)
THE ROLE OF GLP-1 AND GIP (INCREASED BY
DPP-4 INHIBITORS) IS TO INCREASE INSULIN
AND DECREASE GLUCAGON LEVELS
AMYLIN ANALOGUES
AMYLIN ANALOGUES (PRAMLINTIDE) SLOW GASTRIC
EMPTYING AND SUPPRESS GLUCAGON RELEASE, THUS
HELPING TO REGULATE POSTPRANDIAL BLOOD
GLUCOSE
GLUCAGON-LIKE
POLYPEPTIDE-1 ANALOGS
GLUCAGON-LIKE POLYPEPTIDE
1 (GLP-1) ANALOGS
(EXENATIDE, LIRAGLUTIDE)
INCREASE INSULIN AND
DECREASE GLUCAGON
RELEASE
EXCESS HEPATIC GLUCOSE OUTPUT IS
OFTEN SEEN IN DIABETES DUE TO THE
SUPPRESSION OF GLP-1 RELEASE
SGLT-2 INHIBITORS
SGLT-2 INHIBITORS (CANAGLIFLOZIN) BLOCK THE REABSORPTION
OF GLUCOSE IN THE PROXIMAL CONVOLUTED TUBULE BY
INHIBITING THE SGLT-2 SODIUM-GLUCOSE COTRANSPORTER
(RESPONSIBLE FOR ~90% OF GLUCOSE ABSORPTION IN THE
NEPHRON)
SIDE EFFECTS OF SGLT-2 INHIBITORS
INCLUDE GLUCOSURIA AND INCREASED
INCIDENCE OF UTIS AND VAGINAL YEAST
INFECTIONS
THE LAST THREE CLASSES LISTED (DAGS)
ARE NEWER CLASSES OF DIABETES
MEDICATION
OTHER PATHOLOGY
CARCINOID SYNDROME
CARCINOID SYNDROME OCCURS IN LESS THAT 10% OF
PATIENTS WHO HAVE AN ILEAL CARCINOID TUMOR,
THE MOST COMMON MALIGNANCY IN THE SMALL
INTESTINE
CARCINOID TUMORS ARE COMPRISED OF
NEUROENDOCRINE CELLS WHICH SECRETE
VASOACTIVE SUBSTANCES INTO SYSTEMIC
CIRCULATION
SEROTONIN AND KALLIKREIN ARE
VASOACTIVE SUBSTANCES PRODUCED BY
THESE CELLS
SYMPTOMS MANIFEST WHEN THESE SUBSTANCES
GAIN ACCESS TO THE SYSTEMIC CIRCULATION
DISTAL TO THE LIVER
VASOACTIVE SUBSTANCES GAIN ACCESS TO
SYSTEMIC CIRCULATION BY TWO
MECHANISMS:
1) ESCAPING HEPATIC DEGRADATION BY VIRTUE OF
ITS LOCATION (TUMOR METASTASIZES TO LIVER,
TUMOR METASTASIZES TO OR ORIGINATES IN THE
LUNG) OR
2) OVERWHELMING THE LIVER’S CAPACITY
TO METABOLIZE THE VASOACTIVE
SUBSTANCE
WHEN VASOACTIVE SUBSTANCES ENTER THE PORTAL
CIRCULATION, LIVER MONOAMINE OXIDASE [MAO] IS
RESPONSIBLE FOR METABOLIZING SEROTONIN INTO
5-HYDROXYINDOLEACETIC ACID (5-HIAA)
CARCINOID SYNDROME IS STRONGLY ASSOCIATED WITH
METASTATIC DISEASE, BECAUSE THE RESPONSIBLE
NEOPLASTIC GROWTH MUST SECRETE VASOACTIVE
SUBSTANCES INTO NON-PORTAL VENOUS CIRCULATION
SUBSTANCES RELEASED BY TUMORS CONFINED TO
THE INTESTINE ARE METABOLIZED TO INACTIVE
FORMS BY "FIRST PASS" METABOLISM OF THE
LIVER
CARCINOID SYNDROME CAN RARELY BE CAUSED BY
LUNG CARCINOID TUMORS, ISLET CELL
CARCINOMA, AND MEDULLARY THYROID
CARCINOMA
SYMPTOMS INCLUDE:
FLUSHING OF THE SKIN
SECRETORY (WATERY,
VOLUMINOUS) DIARRHEA,
ABDOMINAL CRAMPS WITH
NAUSEA AND VOMITING
WHEEZING, CAUSED BY
BRONCHOCONSTRICTION AND/OR
BRONCHOSPASM
TRICUSPID INSUFFICIENCY OR PULMONIC
VALVE STENOSIS (TIPS)
CARCINOID HEART DISEASE IS CHARACTERIZED BY
PATHOGNOMONIC PLAQUE-LIKE DEPOSITS OF FIBROUS
TISSUE, COMMONLY ON THE ENDOCARDIUM OF VALVULAR
CUSPS AND LEAFLETS
THE RIGHT SIDE OF THE HEART IS AFFECTED BECAUSE THE
LUNGS (LIKE THE LIVER) CONTAIN MAO, WHICH INACTIVATES
HUMORAL SUBSTANCES BEFORE THEY ARE RETURNED TO
THE LEFT HEART
DIAGNOSIS
MADE BY INCREASED URINARY SECRETION
OF 5-HYDROXYINDOLEACETIC ACID (5-HIAA),
A DEGRADATION PRODUCT OF SEROTONIN
TREATED WITH OCTREOTIDE
A SOMATOSTATIN ANALOGUE THAT,
AMONG OTHER THINGS, INHIBITS THE
RELEASE OF SEROTONIN
SURGICAL RESECTION AND CHEMOTHERAPY
WITH 5-FLUOROURACIL AND DOXORUBICIN
ARE OTHER TREATMENT OPTIONS
GASTROENTEROLOGY
PATHOLOGY
CARCINOID
NEUROENDOCRINE TUMOR, MOST COMMON
SMALL BOWEL TUMOR (50%)
COMMON SITES: APPENDIX, SMALL INTESTINE,
RECTUM, STOMACH, COLON
PRODUCE 5HT (SEROTONIN), BUT
ASYMPTOMATIC UNLESS 5HT GETS BEYOND
LIVER’S FIRST-PASS METABOLISM
GENERALLY, IN ORDER FOR SYMPTOMS TO
OCCUR, THE TUMOR MUST METASTASIZE TO
THE LIVER
IF CARCINOID METASTASIZES TO LIVER OR
BEYOND → CARCINOID SYNDROME
(SYMPTOMATIC)
UNCOMMONLY, PRIMARY TUMORS IN THE
BRONCHUS CAN CAUSE SYMPTOMS
WITHOUT METS
CARCINOID SYNDROME IS CHARACTERIZED BY
BRONCHOSPASM, DIARRHEA, AND ERYTHEMA CAUSED
BY THE RELEASE OF SEROTONIN FROM A CARCINOID
TUMOR
CARCINOID HEART DISEASE IS CHARACTERIZED BY
PATHOGNOMONIC PLAQUE-LIKE DEPOSITS OF FIBROUS
TISSUE IN THE VALVES OF THE RIGHT HEART LEADING TO
TRICUSPID VALVE REGURGITATION AND PULMONARY VALVE
STENOSIS
LEFT HEART LESIONS ARE NOT SEEN DUE
TO PULMONARY MONOAMINE OXIDASE
ENZYMES WHICH METABOLIZE SEROTONIN
HEMATOLOGY/ONCOLOGY
HEMATOLOGICAL DISORDERS
OVERVIEW OF ANEMIA
MCV (MEAN CORPUSCULAR VOLUME): ONE
OF THE BEST LAB VALUES USED FOR
CATEGORIZING ANEMIAS
<80 = MICROCYTIC, >100 =
MACROCYTIC. 80-100 =
NORMOCYTIC
THE MICROCYTIC ANEMIAS
INCLUDE (►MNEMONIC:
TAILS):
THALASSEMIAS
THALASSEMIAS WILL ALSO
SHOW TARGET CELLS,
BASOPHILIC STIPPLING
ANEMIA OF CHRONIC
DISEASE
ANEMIA OF CHRONIC
DISEASE COMMONLY
PRESENTS AS MICROCYTIC
ANEMIA
IRON DEFICIENCY ANEMIA
LEAD POISONING
SIDEROBLASTIC ANEMIAS
SIDEROBLASTIC ANEMIA IS
ASSOCIATED WITH
MYELODYSPLASTIC
SYNDROME ("PRE-LEUKEMIA")
AS WELL AS CHRONIC
ALCOHOLISM AND LEAD
POISONING.
THE BEST WAY TO
DIFFERENTIATE BETWEEN THE
MICROCYTIC ANEMIAS IS BY
SERUM FERRITIN LEVELS.
THALASSEMIA: NORMAL IRON
STUDIES
ANEMIA OF CHRONIC
DISEASE: INCREASED
FERRITIN, DECREASED %
SATURATION OF
TRANSFERRIN, DECREASED
SERUM IRON.
IRON DEFICIENCY ANEMIA:
DECREASED FERRITIN
BECAUSE OF DEFICIENT IRON
STORES
MACROCYTIC
(MEGALOBLASTIC) ANEMIAS
ARE CAUSED BY VITAMIN B12
AND FOLATE DEFICIENCIES
OR BY PHARMACOLOGIC
AGENTS THAT INHIBIT DNA
SYNTHESIS (I.E. ZIDOVUDINE
AND PHENYTOIN)
VITAMIN B12 DEFICIENCY IS
MORE CLOSELY ASSOCIATED
WITH NEUROLOGIC
SEQUELAE THAN FOLATE
DEFICIENCY.
HYPERSEGMENTED
NEUTROPHILS ARE SEEN IN
BOTH VITAMIN B12 AND
FOLATE DEFICIENCY.
NOTABLE LABORATORY
FINDINGS IN MACROCYTIC
ANEMIA CAUSED BY VITAMIN
B12 OR FOLATE DEFICIENCY
INCLUDE:
HYPERHOMOCYSTEINEMIA
(VITAMIN B12 AND FOLATE
DEFICIENCY)
METHYLMALONYLACIDEMIA
(VITAMIN B12 DEFICIENCY,
NOT FOLATE DEFICIENCY)
NORMOCYTIC ANEMIAS –
PRETTY MUCH EVERYTHING
ELSE, BUT NOTABLE
EXAMPLES:
ANEMIA OF CHRONIC
DISEASE CAN ALSO CAUSE A
NORMOCYTIC ANEMIA.
LEUKEMIAS AND APLASTIC
ANEMIA
ENZYME DEFECTS (G6PD
DEFICIENCY)
HEMOGLOBINOPATHIES (HBC,
SICKLE CELL), LOOK FOR
TARGET CELLS
HAPTOGLOBIN: BINDS FREE
SERUM HEMOGLOBIN
↓ SERUM HAPTOGLOBIN
SUGGESTS INTRAVASCULAR
HEMOLYSIS (MORE HB
RELEASED INTO SERUM)
↓ HAPTOGLOBIN CAN
SUGGEST LIVER DISEASE
(LIVER CANNOT PRODUCE
NORMAL LEVELS OF
HAPTOGLOBIN)
LDH (LACTATE
DEHYDROGENASE):
ABUNDANT IN RBCS
↑ SERUM LDH CAN SUGGEST
HEMOLYSIS, BUT THIS IS
NONSPECIFIC (NEED MORE
EVIDENCE FOR HEMOLYSIS TO
MAKE THE DIAGNOSIS)
BOTH THE DIRECT
ANTIGLOBULIN TEST (DAT)
AND INDIRECT ANTIGLOBULIN
TEST (IAT) ALSO KNOWN AS
THE DIRECT AND INDIRECT
COOMBS TESTS USE
ANTIGLOBULIN (COOMBS
REAGENT) TO ELUCIDATE
CERTAIN
IMMUNOHEMATOLOGIC
INFORMATION IN THE
CLINICAL SETTING.
ANTIGLOBULIN IS AN
ANIMAL-DERIVED IGM
ANTIBODY SPECIFIC FOR
HUMAN IGG OR HUMAN
COMPLEMENT COMPONENT
C3
THE DAT IS PRIMARILY USED
TO DIAGNOSE
IMMUNE-MEDIATED
HEMOLYTIC ANEMIA. THE DAT
DETECTS RED CELLS THAT
ARE BOUND WITH
ANTIBODIES OR
COMPLEMENT.
THE STEPS OF THE DAT ARE
AS FOLLOWS:
BLOOD SAMPLE IS DRAWN
THE PATIENT’S SERUM IS
REMOVED FROM THE SAMPLE
(LEAVING ONLY THE
PATIENT’S RED CELLS AND
ANY BOUND ANTIBODIES)
ANTIGLOBULIN IS ADDED TO
THE SAMPLE; ANTIGLOBULIN
BINDS ANTIBODIES AND
COMPLEMENT ON THE
PATIENT'S RED CELLS,
CAUSING AGGLUTINATION
(POSITIVE RESULT)
A POSITIVE DAT SUGGESTS
AN IMMUNE-MEDIATED
HEMOLYTIC ANEMIA.
THE IAT IS PRIMARILY USED TO
SCREEN FOR BLOOD TYPE
COMPATIBILITY PRIOR TO
TRANSFUSION. THE IAT
DETECTS UNBOUND
ANTIBODIES AGAINST
CERTAIN TYPES OF RBC
ANTIGENS.
THE STEPS OF THE IAT ARE AS
FOLLOWS:
BLOOD SAMPLE IS DRAWN
THE PATIENT’S CELLS
(INCLUDING RED CELLS) ARE
REMOVED FROM THE SAMPLE
(LEAVING ONLY THE
PATIENT’S SERUM)
REAGENT RBCS ARE ADDED
TO THE SERUM
THE PATIENT’S ANTIBODIES
BIND ANTIGENS ON THE
REAGENT RBCS FOR WHICH
THEY HAVE SPECIFICITY
ANTIGLOBULIN IS ADDED TO
THE SAMPLE; ANTIGLOBULIN
BINDS THE PATIENT’S
ANTIBODIES AND
COMPLEMENT ON THE
REAGENT RBCS, CAUSING
AGGLUTINATION (POSITIVE
RESULT)
A POSITIVE IAT SUGGESTS AN
INCOMPATIBILITY TO
TRANSFUSION WITH THE
REAGENT RBCS.
A CROSSMATCH TEST IS
SIMPLY A TYPE OF IAT IN
WHICH THE REAGENT RBCS
COME FROM A UNIT OF
BLOOD THAT IS INTENDED
TO BE TRANSFUSED
THROMBOTIC
MICROANGIOPATHIES
DISORDERS CHARACTERIZED BY
CONSUMPTION OF PLATELETS INTO
SMALL VESSEL MICROTHROMBI
MICROANGIOPATHIC
HEMOLYTIC ANEMIA
THE MOST COMMON TYPES ARE
THROMBOTIC THROMBOCYTOPENIC
PURPURA AND HEMOLYTIC-UREMIC
SYNDROME
THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) IS
CHARACTERIZED BY THROMBOCYTOPENIA AND
MICROANGIOPATHIC HEMOLYTIC ANEMIA WITH THE TRIAD OF
FEVER, TRANSIENT NEUROLOGICAL DEFICITS, AND RENAL
FAILURE
THE HEMOLYTIC-UREMIC SYNDROME (HUS) IS
CHARACTERIZED BY THE SIMULTANEOUS OCCURRENCE OF
THROMBOCYTOPENIA, MICROANGIOPATHIC HEMOLYTIC
ANEMIA, AND ACUTE KIDNEY INJURY
THE MOST COMMON CAUSE OF HUS IS
VEROTOXIN-PRODUCING (SHIGA-LIKE TOXIN)
ESCHERICHIA COLI
NOTABLE LABORATORY
FINDINGS IN TTP AND HUS
INCLUDE:
NORMAL PROTHROMBIN TIME (PT/INR)
AND PARTIAL THROMBOPLASTIN TIME
(PTT)
INCREASED BLEEDING TIME
INCREASED
MEGAKARYOCYTES ON BONE
MARROW BIOPSY
ANEMIA WITH SCHISTOCYTES
ON PERIPHERAL BLOOD
SMEAR
THROMBOCYTOPENIA
HEMATOLOGIC MALIGNANCIES
LYMPHOMA: NON-HODGKIN
NON-HODGKIN LYMPHOMA (NHL) ENCOMPASSES THE
LYMPHOMA SUBTYPES CHARACTERIZED BY MALIGNANCY OF
LYMPHOID CELLS (AS OPPOSED TO REED-STERNBERG CELLS
IN HODGKIN LYMPHOMA)
NHLS FREQUENTLY EXHIBIT DIFFUSE,
EXTRANODAL SPREAD (WHICH IS RARELY
SEEN IN HL)
NHLS PRESENT MAINLY IN LATE
ADULTHOOD, WITH SOME EXCEPTIONS (AS
OPPOSED TO YOUNG ADULTHOOD IN HL)
NHLS MAY HAVE AN OVERT “LEUKEMIC
PHASE” OR CIRCULATION OF NEOPLASTIC
CELLS IN PERIPHERAL BLOOD (WHICH IS NOT
SEEN IN HL)
NHLS ARE CATEGORIZED INTO INDOLENT
(LOW-GRADE) AND AGGRESSIVE
(HIGH-GRADE) TYPES
THE NOTABLE NHL SUBTYPES
INCLUDE:
FOLLICULAR LYMPHOMA
(MOST COMMON INDOLENT
NHL)
FOLLICULAR LYMPHOMA IS AN
INDOLENT NHL
IN FOLLICULAR LYMPHOMA, THERE IS A
MALIGNANCY OF GERMINAL-CENTER
DERIVED SMALL CD20+ B CELLS
IT IS ASSOCIATED WITH A TRANSLOCATION,
T(14;18) THAT LEADS TO OVEREXPRESSION
OF THE ANTI-APOPTOSIS PROTEIN BCL2
FOLLICULAR LYMPHOMA SHOULD BE DISTINGUISHED FROM
FOLLICULAR HYPERPLASIA ON THE BASIS OF
MONOCLONALITY, FOLLICULAR BCL2 EXPRESSION, AND
ABSENCE OF TINGIBLE BODY MACROPHAGES IN GERMINAL
CENTERS
MANTLE CELL LYMPHOMA
MANTLE CELL LYMPHOMA IS
AN AGGRESSIVE NHL
IN MANTLE CELL LYMPHOMA, THERE IS USUALLY A
MALIGNANCY OF SMALL CD5+ AND CD23B CELLS THAT
EXPANDS THE MANTLE ZONE OF GERMINAL CENTER
FOLLICLES
IT IS ASSOCIATED WITH A TRANSLOCATION, T(11;14) THAT
LEADS TO OVEREXPRESSION OF CELL CYCLE-REGULATING
PROTEIN CYCLIN D1 WHICH PROMOTES THE G1 TO S
TRANSITION
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) IS
ALSO A NEOPLASM OF SMALL TO
MEDIUM-SIZED LYMPHOID CELLS
BOTH ARE POSITIVE FOR CD5 AND CD20,
HOWEVER, CLL IS POSITIVE FOR CD23 WHILE
MANTLE CELL LYMPHOMA IS NEGATIVE FOR
CD23
MANTLE CELL LYMPHOMA
GENERALLY HAS THE WORST
PROGNOSIS OF ALL THE NHLS
MARGINAL ZONE LYMPHOMA
MARGINAL ZONE LYMPHOMA
IS AN INDOLENT NHL
IN MARGINAL ZONE LYMPHOMA, THERE IS A MALIGNANCY
OF SMALL CD20+ B CELLS THAT EXPANDS THE OUTER
LAYER (“MARGINAL ZONE”) OF THE MANTLE OF GERMINAL
CENTER FOLLICLES
IT IS ASSOCIATED WITH SJÖGREN’S
SYNDROME, HASHIMOTO THYROIDITIS, AND
HELICOBACTER PYLORI GASTRITIS
MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA
(MALTOMA) IS A TYPE OF MARGINAL ZONE
LYMPHOMA ASSOCIATED WITH HELICOBACTER
PYLORI INFECTION
BURKITT LYMPHOMA
BURKITT LYMPHOMA IS AN
AGGRESSIVE NHL
IN BURKITT LYMPHOMA, THERE IS A MALIGNANCY OF
INTERMEDIATE-SIZED CD20+ B CELLS THAT CLASSICALLY INVOLVES THE
JAW (ENDEMIC FORM FOUND MOSTLY IN AFRICAN CHILDREN) OR THE
ILEOCECAL REGION OF THE GI TRACT (SPORADIC AND
IMMUNODEFICIENCY FORMS)
IT IS ASSOCIATED WITH A TRANSLOCATION,
T(8;14) THAT LEADS TO OVEREXPRESSION
OF THE C-MYC ONCOGENE
INFECTION WITH EPSTEIN-BARR VIRUS (EBV) HAS BEEN
IMPLICATED IN THE PATHOGENESIS OF BURKITT LYMPHOMA
WITH THE STRONGEST ASSOCIATION TO THE ENDEMIC
FORM
IN TUMORS OF BURKITT LYMPHOMA, THE RELATIVELY CLEAR
FORM OF THE REACTIVE HISTIOCYTES IN A BACKDROP OF
BLUE NEOPLASTIC CELLS IMPARTS A CLASSIC “STARRY SKY”
APPEARANCE ON HISTOLOGY
IN CONTRAST TO OTHER B-CELL
LYMPHOMAS, THESE TUMORS USUALLY FAIL
TO EXPRESS BCL2
DIFFUSE LARGE B-CELL
LYMPHOMA (MOST COMMON
NHL OVERALL)
DIFFUSE LARGE B-CELL
LYMPHOMA (DLBCL) IS AN
AGGRESSIVE NHL
IN DLBCL, THERE IS A MALIGNANCY OF
LARGE, TRANSFORMED CD20+ B
CELLS
IT IS ASSOCIATED WITH TRANSLOCATIONS OR
MUTATIONS DURING SOMATIC HYPERMUTATION THAT
LEADS TO OVEREXPRESSION OF THE ANTI-APOPTOSIS
PROTEIN BCL6
SOME TUMORS ALSO EXHIBIT EXPRESSION
OF SURFACE IMMUNOGLOBULIN AND
BCL2
DLBCL IS THE MOST
COMMON NHL
ADULT T-CELL
LYMPHOMA/LEUKEMIA
ADULT T-CELL LYMPHOMA/LEUKEMIA (ATLL) IS AN
AGGRESSIVE NHL CAUSED BY INFECTION OF CD4+
T-CELLS BY HUMAN T-LYMPHOTROPIC VIRUS 1
(HTLV-1)
THE RISK OF DEVELOPING ATLL AS A RESULT
OF INFECTION IS EXTREMELY LOW AND THE
LATENCY PERIOD IS OFTEN SEVERAL
DECADES
CUTANEOUS T-CELL
LYMPHOMAS (I.E. MYCOSIS
FUNGOIDES)
MYCOSIS FUNGOIDES (MF) IS AN INDOLENT
CUTANEOUS T-CELL NHL OF
DERMATOTROPHIC CD4+ T-CELLS
SÉZARY SYNDROME IS A GENERALIZED
EXFOLIATIVE DERMATITIS THAT REPRESENTS
A MORE AGGRESSIVE, LEUKEMIC FORM OF
MF
THIS VARIANT IS CHARACTERIZED BY A
LEUKEMIA OF SÉZARY CELLS WITH
CEREBRIFORM NUCLEI
HEMOSTASIS
THROMBOCYTOPENIA
THROMBOCYTOPENIA DESCRIBES A CONDITION IN WHICH
THERE IS A BELOW-NORMAL LEVEL OF PLATELETS. IT
USUALLY RESULTS FROM ONE OR A COMBINATION OF THE
FOLLOWING CAUSES:
DECREASED BONE MARROW
PRODUCTION
SEQUESTRATION (USUALLY IN
THE SPLEEN)
INCREASED PLATELET CONSUMPTION
OR DESTRUCTION
ACUTE IDIOPATHIC THROMBOCYTOPENIC PURPURA
(ACUTE ITP) IS AN AUTOIMMUNE DISORDER
CHARACTERIZED BY DEVELOPMENT OF IGG ANTIBODIES
AGAINST THE GPIIB/IIIA RECEPTOR. IT OCCURS MOST
OFTEN IN CHILDREN 1-2 WEEKS FOLLOWING A VIRAL
INFECTION
NOTABLE SIGNS AND SYMPTOMS OF ACUTE ITP INCLUDE
SUDDEN APPEARANCE OF A PETECHIAL RASH, EASY BRUISING, OR
BLEEDING IN AN OTHERWISE HEALTHY CHILD
SPLENOMEGALY AND LYMPHADENOPATHY
ARE NOT PRESENT
NOTABLE LABORATORY FINDINGS IN
ACUTE ITP INCLUDE:
THROMBOCYTOPENIA
INCREASED MEGAKARYOCYTES ON
BONE MARROW BIOPSY
LARGE PLATELETS ON
PERIPHERAL BLOOD SMEAR
PROTHROMBIN TIME (PT/INR) AND PARTIAL THROMBOPLASTIN
TIME (PTT) ARE NORMAL
TREATMENT FOR ACUTE ITP IS RARELY GIVEN (IT IS MOSTLY
SELF-LIMITING), EXCEPT IN CASES WHERE THROMBOCYTOPENIA IS
SEVERE. CONVENTIONAL DRUG TREATMENT FOR ACUTE ITP IS WITH
CORTICOSTEROIDS
CHRONIC IDIOPATHIC THROMBOCYTOPENIC
PURPURA (CHRONIC ITP) IS AN AUTOIMMUNE
DISORDER CHARACTERIZED BY DEVELOPMENT OF
IGG ANTIBODIES AGAINST THE GPIIB/IIIA RECEPTOR
CHRONIC ITP OCCURS MOST
OFTEN IN ADULT WOMEN
NOTABLE SIGNS AND SYMPTOMS OF CHRONIC
ITP INCLUDE PETECHIAL RASH OR
ECCHYMOSES, EASY BRUISING, OR BLEEDING
SPLENOMEGALY AND LYMPHADENOPATHY ARE
UNCOMMON FINDINGS IN THE IDIOPATHIC
(PRIMARY FORM) THEIR PRESENCE SUGGESTS ITP
SECONDARY TO A B-CELL NEOPLASM
NOTABLE LABORATORY FINDINGS
IN CHRONIC ITP INCLUDE:
THROMBOCYTOPENIA
INCREASED MEGAKARYOCYTES ON
BONE MARROW BIOPSY
LARGE PLATELETS ON
PERIPHERAL BLOOD SMEAR
PROTHROMBIN TIME (PT/INR) AND PARTIAL
THROMBOPLASTIN TIME (PTT) ARE NORMAL
CONVENTIONAL TREATMENTS FOR
CHRONIC ITP INCLUDE:
CORTICOSTEROIDS (AS AN
IMMUNOSUPPRESSANT)
IV IMMUNOGLOBULIN (TO
INCREASE PLATELET COUNT)
SEVERE OR REFRACTORY CASES:
SPLENECTOMY (TO ELIMINATE SITE OF
PLATELET DESTRUCTION)
THROMBOTIC MICROANGIOPATHIES ARE DISORDERS
CHARACTERIZED BY THE CONSUMPTION OF
PLATELETS INTO SMALL VESSEL MICROTHROMBI AND
HEMOLYTIC ANEMIA. THE MOST COMMON TYPES
ARE THROMBOTIC THROMBOCYTOPENIC PURPURA
(TTP) AND HEMOLYTIC-UREMIC SYNDROME (HUS)
TTP IS CAUSED BY DEFICIENCY OF ADAMTS13 (VON
WILLEBRAND FACTOR METALLOPROTEASE), WHICH
NORMALLY DEGRADES VWF MULTIMERS. THIS IS
USUALLY DUE TO DEVELOPMENT OF ANTI-ADAMTS13
AUTOANTIBODIES
THE FORMATION OF MICROTHROMBI IN TTP IS DUE TO
ACCUMULATION OF LARGE, UNCLEAVED VWF MULTIMERS
WHICH ARE THOUGHT TO CONTRIBUTE TO EXCESSIVE
PLATELET ADHESION AND AGGREGATION
HUS IS CAUSED BY DAMAGE TO ENDOTHELIAL
CELLS, LEADING TO PLATELET ADHESION
AND MICROTHROMBI FORMATION
HUS OCCURS MOST OFTEN IN CHILDREN, ESPECIALLY FOLLOWING
GASTROINTESTINAL ILLNESS WITH INFLAMMATORY DIARRHEA HUS
IS HIGHLY ASSOCIATED WITH GASTROENTERITIS CAUSED BY THE
SHIGA-LIKE TOXIN OF ESCHERICHIA COLI O157:H7
ATYPICAL HUS IS ASSOCIATED WITH
ALTERNATIVE COMPLEMENT PATHWAY INHIBITOR
DEFICIENCIES. DRUG-INDUCED HUS IS
ASSOCIATED WITH QUININE AND SOME
CHEMOTHERAPY AGENTS
NOTABLE SIGNS AND SYMPTOMS OF TTP
AND HUS INCLUDE:
MICROANGIOPATHIC
HEMOLYTIC ANEMIA
THROMBOCYTOPENIA
FEVER
NEUROLOGIC DEFECTS
(MOSTLY TTP)
ACUTE RENAL FAILURE PRECEDED
BY INFLAMMATORY DIARRHEA (HUS)
NOTABLE LABORATORY FINDINGS IN
TTP AND HUS INCLUDE:
THROMBOCYTOPENIA
INCREASED BLEEDING TIME
INCREASED MEGAKARYOCYTES ON
BONE MARROW BIOPSY
ANEMIA WITH SCHISTOCYTES ON
PERIPHERAL BLOOD SMEAR
PROTHROMBIN TIME (PT/INR) AND PARTIAL
THROMBOPLASTIN TIME (PTT) ARE NORMAL
TREATMENT FOR TTP AIMS TO REMOVE AUTOANTIBODIES
TO ADAMTS13 AND RESUPPLY THE PLASMA WITH DONOR
ADAMTS13
TREATMENT FOR TYPICAL HUS IS USUALLY SUPPORTIVE.
TREATMENT FOR ATYPICAL HUS AIMS TO INHIBIT
COMPLEMENT FACTOR ACTIVATION
CONVENTIONAL TREATMENTS FOR TTP
AND HUS INCLUDE:
PLASMA EXCHANGE (MOSTLY TPP – REMOVES
AUTOANTIBODIES, ADDS DONOR ADAMTS13)
DIALYSIS OR RENAL TRANSPLANT (MOSTLY HUS – IN CASES
WHERE THERE IS EXTENSIVE RENAL DAMAGE)
ECULIZUMAB (ATYPICAL HUS – INHIBITS CLEAVAGE
OF COMPLEMENT COMPONENT C5 TO C5A AND
C5B, PREVENTING TERMINAL COMPLEMENT
ACTIVATION)
OTHER IMMUNOSUPPRESSIVE AGENTS
ANTIPHOSPHOLIPID SYNDROME
ALSO KNOWN AS LUPUS
ANTICOAGULANT SYNDROME
IT IS A COMMONLY TESTED
ACQUIRED THROMBOPHILIA
THE ANTIPHOSPHOLIPID SYNDROME (OR ANTIPHOSPHOLIPID ANTIBODY
SYNDROME) IS A HYPERCOAGULABLE STATE CHARACTERIZED BY THE
PRESENCE OF AT LEAST ONE TYPE OF AUTOANTIBODY KNOWN AS AN
ANTIPHOSPHOLIPID ANTIBODY
CURRENTLY RECOGNIZED
ANTIPHOSPHOLIPID ANTIBODIES INCLUDE
THE FOLLOWING:
ANTICARDIOLIPIN
ANTIBODIES
ANTIBODIES TO
Β-2-GLYCOPROTEIN-I
LUPUS ANTICOAGULANT
IN THE BLOOD STREAM, ANTIBODIES
DIRECTLY ACTIVATE PLATELETS AND
COMPLEMENT
→ HYPERCOAGULABLE STATE
PATIENTS COMMONLY PRESENT WITH A
HISTORY OF RECURRENT DVT AND
MISCARRIAGES
THESE AUTOANTIBODIES CAN
INTERFERE WITH PLACENTA
FORMATION
IN VITRO, THE ANTIBODIES INTERFERE WITH
PHOSPHOLIPIDS (HENCE ANTIPHOSPHOLIPID)
AND INHIBIT COAGULATION → ↑ PTT
ADDITIONALLY, ANTIPHOSPHOLIPID
ANTIBODIES CAN CAUSE A FALSE
POSITIVE FOR SYPHILIS
ORTHOPEDICS & RHEUMATOLOGY
PULMONOLOGY
PATHOLOGY
NASOPHARYNGEAL DISORDERS
RHINITIS IS IRRITATION AND INFLAMMATION OF
THE MUCOUS MEMBRANE INSIDE THE NOSE THAT
CAN BE CHARACTERIZED AS ALLERGIC OR
INFECTIOUS
THE ATOPIC TRIAD IN CHILDREN IS
CHARACTERIZED BY
RHINITIS
ASTHMA
ATOPIC DERMATITIS
ALLERGIC RHINITIS IS CAUSED BY A TYPE I
HYPERSENSITIVITY REACTION AND IS
CHARACTERIZED BY AN INFLAMMATORY
INFILTRATE WITH EOSINOPHILS
ALLERGIC RHINITIS PRESENTS
WITH
SNEEZING
NASAL ITCHING
RHINORRHEA
HISTORY OF ALLERGIC RHINITIS IS
IMPORTANT IN DISTINGUISHING BETWEEN
ATOPIC AND NON-ATOPIC ASTHMA
CHURG-STRAUSS SYNDROME IS A SMALL VESSEL
NECROTIZING VASCULITIS ASSOCIATED WITH ALLERGIC
RHINITIS ALONG WITH ASTHMA, LUNG INFILTRATES, AND
PERIPHERAL EOSINOPHILIA
TREATMENT INCLUDES AVOIDING ALLERGIC TRIGGERS,
INTRANASAL CORTICOSTEROIDS (MOST EFFECTIVE
TREATMENT), ANTIHISTAMINES, LEUKOTRIENE
INHIBITORS, IPRATROPIUM BROMIDE, AND CROMOLYN
INFECTIOUS RHINITIS IS
CAUSED BY INFECTION OF
THE NASAL MUCOSA
MOST COMMON CAUSE OF
INFECTIOUS RHINITIS IS
RHINOVIRUS
SYMPTOMS OF INFECTIOUS
RHINITIS INCLUDE
SNEEZING
NASAL CONGESTION
RHINORRHEA
SORE THROAT
DRY COUGH
TREATMENT OF INFECTIOUS RHINITIS WITH
ANTIBIOTICS IS NOT INDICATED. TREATMENT
IS SUPPORTIVE, HOWEVER COLD
PREPARATIONS SHOULD BE AVOIDED IN
CHILDREN UNDER THE AGE OF 4
CHOANAL ATRESIA IS THE MOST COMMON CONGENITAL
ANOMALY OF THE NOSE AND IS CAUSED BY FAILURE OF
THE NASAL PASSAGE TO CANALIZE DURING
DEVELOPMENT
CHOANAL ATRESIA AFFECTS
FEMALES TWICE AS OFTEN AS
MALES
AS A RESULT OF FAILED CANALIZATION,
ABNORMAL BONY (90%) OR SOFT TISSUE
(MEMBRANOUS TYPE-10%) IS PRESENT
CHOANAL ATRESIA CAN BE UNILATERAL OR
BILATERAL, WITH THE BILATERAL TYPE COMMONLY
ASSOCIATED WITH OTHER CONGENITAL
ABNORMALITIES
A NEWBORN THAT BECOMES CYANOTIC
DURING BREASTFEEDING THAT RESOLVES
AFTER CRYING IS INDICATIVE OF CHOANAL
ATRESIA
ADENOIDITIS IS INFLAMMATION OF THE
ADENOID TISSUE AND IS MOST COMMONLY SEEN
IN CHILDREN, ALTHOUGH IT CAN OCCUR IN
ADULTS
ADENOIDS BEGIN DECREASING IN SIZE BY AGE 5-6, AND
OFTEN DISAPPEAR BY THE TEENAGE YEARS. THEY
FUNCTION TO TRAP PATHOGENS AND PRODUCE
ANTIBODIES TO FIGHT INFECTION
ADENOIDITIS IS TYPICALLY VIRAL IN
NATURE, BUT CAN ALSO BE
BACTERIAL
COMMON VIRAL CAUSES OF
ADENOIDITIS ARE
ADENOVIRUS
RHINOVIRUS
PARAMYXOVIRUS
COMMON BACTERIAL CAUSES
OF ADENOIDITIS ARE
S. PYOGENES
S. PNEUMONIA
M. CATARRHALIS
S. AUREUS
PATIENTS WITH ADENOIDITIS
CAN PRESENT WITH
SORE THROAT
RHINORRHEA
FEVER
AIRWAY OBSTRUCTION
EAR PAIN
TREATMENT INVOLVES
STEROIDAL SPRAY (TO
REDUCE CONGESTION)
ANTIBIOTICS (IF BACTERIAL
ETIOLOGY)
SURGICAL REMOVAL OF
ADENOIDS
OFTEN THE TONSILS ARE
REMOVED AT THE SAME TIME
FOR RECURRENT INFECTION
NASAL POLYPS ARE NON-NEOPLASTIC EDEMATOUS
PROTRUSIONS IN THE LINING OF THE NASAL CAVITY,
AND ARE A RESPONSE TO CHRONIC
INFLAMMATION
ALLERGIC POLYPS ARE THE MOST COMMON TYPE OF
NASAL POLYP. DEVELOPMENT OF ALLERGIC POLYPS IS AN
IGE MEDIATED PROCESS, AND EOSINOPHILS ARE SEEN ON
PERIPHERAL SMEAR
NASAL POLYPS CAN BE SEEN IN PEDIATRIC PATIENTS WITH
CYSTIC FIBROSIS (CF). THE THICK SECRETIONS IN CF CAUSE
POLYPS TO FORM. A SWEAT-CHLORIDE TEST IS INDICATED IN
CHILDREN WITH NASAL POLYPS TO RULE OUT CF
SIXTY TO SEVENTY PERCENT OF ADULT
PATIENTS WHO HAVE A HYPERSENSITIVITY
TO ASPIRIN HAVE NASAL POLYPS
ANGIOFIBROMA IS A BENIGN
VASCULAR TUMOR
THE CLASSIC PATIENT FOR AN
ANGIOFIBROMA IS AN ADOLESCENT MALE
WITH RECURRENT NOSEBLEEDS
PATIENTS TYPICALLY PRESENT WITH
UNILATERAL NASAL OBSTRUCTION AND
HISTORY OF RECURRENT NOSEBLEEDS
IMAGING SUCH AS CT AND MRI HELP SHOW THE
EXTENT OF THE TUMOR. ANGIOGRAPHY HELPS
IDENTIFY WHAT VESSELS THE TUMOR ORIGINATED
FROM
TREATMENT INVOLVES HORMONAL
THERAPY, RADIATION, AND/OR SURGICAL
REMOVAL
NASOPHARYNGEAL CARCINOMA IS THE MOST
COMMON CANCER OF THE NASOPHARYNX AND IS
STRONGLY ASSOCIATED WITH EPSTEIN-BARR VIRUS (EBV)
INFECTION
THIS CONDITION HAS A HIGH
PREVALENCE AMONGST
CHINESE PATIENTS, AND IS
MOSTLY FOUND IN MALES
THE THREE SUB-TYPES OF
NASOPHARYNGEAL
CARCINOMA ARE
SQUAMOUS CELL
CARCINOMA (SCC)
NONKERATINIZING
SQUAMOUS CARCINOMA
UNDIFFERENTIATED CANCER
PRESENTING SYMPTOMS
DEPEND ON THE LOCATION
OF THE TUMOR, AND MAY
INCLUDE
OBSTRUCTION
DISCHARGE
EPISTAXIS
DIZZINESS
TINNITUS
DIPLOPIA
HORNER’S SYNDROME
NASOPHARYNGEAL
CARCINOMA METASTASIZES
TO THE CERVICAL LYMPH
NODES IN 70% OF CASES
DIAGNOSIS CAN BE BASED
OFF OF
CT-SCAN
SKULL X-RAY
RIGID ENDOSCOPY
POSTERIOR RHINOSCOPY
RADIOTHERAPY IS THE TREATMENT OF
CHOICE, AND HAS A 5-YEAR SURVIVAL
RATE OF 50%
PHYSIOLOGY
OXYGEN-HEMOGLOBIN
DISSOCIATION CURVE
THE POSITION OF THE OXYHEMOGLOBIN CURVE IS BEST DESCRIBED BY
THE PO2 AT WHICH HEMOGLOBIN IS 50% SATURATED. THIS IS DEFINED BY
THE P50 VALUE. THE CURVE IS A PLOT OF % SATURATION OF
HEMOGLOBIN AS A FUNCTION OF PO2
THE NORMAL VALUE FOR P50
IS 26.7MMHG
WHEN P50 > 26.7MMHG, THE HEMOGLOBIN
DISSOCIATION CURVE IS SAID TO HAVE
"SHIFTED TO THE RIGHT"
TRANSLATES TO → "WHEN 50%
HEMOGLOBIN SATURATION OCCURS AT
PO2 > 26.7 MMHG"
WITH A "RIGHT SHIFT" → HEMOGLOBIN HAS
LESS AFFINITY FOR O2 → FACILITATES
UNLOADING OF O2 TO TISSUES
RIGHT SHIFT OCCURS WITH:
↑ TEMPERATURE → CAN OCCUR
PATHOLOGICALLY OR NORMALLY (LOCALLY
IN THE MUSCLES DURING EXERCISE)
↑ [H+] / ↓ PH
HIGHER ALTITUDE
↑ 2,3-BPG (AKA 2,3-DPG), AND
CHRONIC ANEMIA → VIA ↑
2,3-BPG
CAN BE REMEMBERED WITH
MNEMONIC: “CADETs face
RIGHT”
CO2 ↑
ACIDOSIS, ANEMIA
2,3-DPG
ELEVATION
TEMPERATURE ↑
WHEN P50 < 26.7 MMHG → THE
HEMOGLOBIN DISSOCIATION CURVE IS SAID
TO "SHIFT TO THE LEFT"
LEFT SHIFT → REFLECTS AN INCREASE IN
HEMOGLOBIN'S AFFINITY FOR O2 →
FACILITATES LOADING OF O2 IN THE LUNGS
OCCURS WITH:
↓ TEMPERATURE
CO POISONING
↓ [H+]
↓ [2,3-BPG]
FETAL HB
NOTE THE SIGMOIDAL SHAPE
OF THE CURVE AS A RESULT
OF POSITIVE COOPERATIVITY
EACH OXYGEN MOLECULE BOUND TO
HEMOGLOBIN RESULTS IN HIGHER AFFINITY
FOR SUBSEQUENT OXYGEN MOLECULE
BINDING
REPRODUCTIVE
ANATOMY
PROSTATE
LIGAMENTS OF THE UTERUS
GONADAL DRAINAGE
UTERINE TUBES
VAGINA
TESTES
EXTERNAL GENITALIA FEMALE
UTERUS
EXTERNAL GENITALIA MALE
OVARIES
ALMOND-SHAPED ORGANS RESPONSIBLE FOR THE
DEVELOPMENT OF FEMALE OOCYTES AND SECRETION OF
HORMONES, MOST NOTABLY ESTROGEN
LOCATED BILATERALLY IN THE HYPOGASTRIC REGIONS, POSTERIOR
TO THE BROAD LIGAMENT OF THE UTERUS
CLINICAL CORRELATE:
KRUKENBERG TUMORS
METASTATIC TUMORS TO THE OVARIES
THEY USUALLY ARISE FROM CANCERS OF THE BREAST OR GI
TRACT, MOST COMMONLY GASTRIC CANCER
OFTEN PALPABLE
CHARACTERISTIC “SIGNET RING” APPEARANCE
ON MICROSCOPIC EXAMINATION
COVERED BY A SIMPLE CUBOIDAL
EPITHELIUM, ALSO REFERRED TO AS
GERMINAL EPITHELIUM
OUTER CORTEX AND INNER MEDULLA
THE CORTEX CONTAINS DEVELOPING FOLLICLES, WHICH UPON
RUPTURE WILL BECOME THE CORPUS LUTEUM
FOLLICLES PRIMARILY CONSIST OF FOUR CELL LAYERS:
OOCYTES
FOLLICULAR CELLS
GRANULOSA CELLS
THECAL CELLS (EXTERNA AND INTERNA LAYERS)
THE PRIMARY FOLLICLE RUPTURES DURING OVULATION TO RELEASE THE
SECONDARY OOCYTE INTO THE PERITONEAL SPACE. THE RUPTURED
OVARIAN FOLLICLE THEN FORMS THE CORPUS LUTEUM
THE MEDULLA IS COMPOSED OF CONNECTIVE TISSUE THAT
CONTAINS THE ARTERIAL VASCULATURE AND VENOUS DRAINAGE
OF THE OVARY
BLOOD SUPPLY
OVARIAN ARTERIES (GONADAL ARTERIES), WHICH ARE
BRANCHES OF THE ABDOMINAL AORTA
ALSO COLLATERAL FLOW FROM THE
UTERINE ARTERIES, BRANCHES OF THE
INTERNAL ILIAC ARTERIES
THE RIGHT OVARIAN VEIN DRAINS DIRECTLY INTO THE IVC, WHEREAS
THE LEFT OVARIAN VEIN DRAINS INTO THE LEFT RENAL VEIN
CERVIX
STEP 2 CK
INTERNAL MEDICINE
DERMATOLOGY
STEVEN-JOHNSON SYNDROME
STEVENS-JOHNSON SYNDROME (SJS) IS A SEVERE FORM OF
ERYTHEMA MULTIFORME INVOLVING MUCOUS MEMBRANES AND
SEVERE PLAQUE FORMATION. IT IS AN IMMUNE-MEDIATED
HYPERSENSITIVITY REACTION THAT LEADS TO NECROSIS AND
SLOUGHING OF THE EPIDERMIS
STEVENS-JOHNSON SYNDROME
REPRESENTS THE SAME PROCESS AS TOXIC
EPIDERMAL NECROLYSIS (TEN)
INVOLVEMENT OF <10% OF THE BODY
SURFACE IS DIAGNOSED AS SJS
INVOLVEMENT OF >30% IS
DIAGNOSED AS TEN
INVOLVEMENT IN BETWEEN IS
DIAGNOSED AS SJS/TEN
THERE ARE 4 ETIOLOGIC
CATEGORIES FOR SJS:
MEDICATIONS (MOST COMMON) (E.G. PENICILLIN,
SULFA CONTAINING DRUGS, NSAIDS,
ALLOPURINOL, PHENYTOIN, AND
CARBAMAZEPINE)
INFECTIONS (HIV, HEPATITIS)
MALIGNANCY
IDIOPATHIC
SJS PRESENTS WITH A 2-3 DAY PRODROMAL PERIOD OF FEVER
AND FLU-LIKE SYMPTOMS PRIOR TO THE DEVELOPMENT OF
MUCOCUTANEOUS LESIONS
AFTER THE PRODROMAL PERIOD, A PALPABLE
MACULAR RASH WILL BEGIN TO APPEAR, AND THEN
FLUID FILLED BLISTERS AND ULTIMATELY SLOUGHING
OF THE SKIN
IN A PATIENT’S FIRST DRUG-EXPOSURE RELATED CASE OF SJS, THE
DRUG EXPOSURE TYPICALLY OCCURS ONE TO THREE WEEKS
BEFORE THE DEVELOPMENT OF SYMPTOMS
THE TIME COURSE FROM PRODROME UNTIL
HOSPITAL DISCHARGE RANGES BETWEEN
TWO TO FOUR WEEKS
BLISTERING AND SWELLING OF THE ORAL CAVITY
IS ALSO SEEN IN PATIENTS WITH SJS
THERE ARE NO SPECIFIC DIAGNOSTIC STUDIES FOR SJS,
BUT A HISTORY SUGGESTIVE OF DRUG EXPOSURE/ILLNESS,
POSITIVE CLINICAL SYMPTOMS, AND A SKIN BIOPSY CAN
HELP CONFIRM CLINICAL SUSPICION
ON PHYSICAL EXAMINATION A PATIENT WITH SJS WILL
TYPICALLY HAVE AN ERYTHEMATOUS RASH WHICH MAY HAVE
THE APPEARANCE OF A TARGET
OTHER SIGNS THAT RAISE
CONCERN OF SJS INCLUDE:
PALPABLE RASH
BLISTERS
SKIN SLOUGHING
TONGUE SWELLING
ORAL AND LIP ULCERATIONS
LESIONS TYPICALLY START ON THE FACE
AND THORAX BEFORE SPREADING, AND
SPARE THE SCALP
AFTER A FEW DAYS, THE SKIN RASHES
PROGRESSES TO VESICLES AND BULLAE,
AND THE SKIN BEGINS TO SLOUGH
NIKOLSKY SIGN (GENTLE LATERAL PRESSURE ON
SKIN SURFACE ON AN APPARENTLY UNINVOLVED
SITE WHICH CAUSES SLOUGHING) MAY BE
POSITIVE
MUCOUS MEMBRANES ARE ALMOST ALWAYS INVOLVED IN SJS,
INCLUDING THE ORAL MUCOSA (INCLUDING TONGUE), CONJUNCTIVA,
URETHRA, AND PULMONARY MUCOSA
PATIENTS PRESENT WITH CRUSTING AND
ULCERATION OF THE MUCOSAL
SURFACE
SKIN BIOPSIES ARE FAIRLY SPECIFIC AND TYPICALLY SHOW
LYMPHOCYTES WITHIN PERIVASCULAR STRUCTURES AND
FULL THICKNESS EPIDERMAL DETACHMENT WITH A
NORMAL IMMUNOFLUORESCENCE
THE MORTALITY RATE OF SJS
IS ABOUT 10%
IN THOSE WHO SURVIVE, SJS CAN RESULT IN
COMPLICATIONS INVOLVING THE SKIN,
EYES, MOUTH, GU SYSTEM, AND LUNGS
AN EARLY SJS COMPLICATION IS
SECONDARY BACTERIAL INFECTION
LATER DERMATOLOGIC SEQUELAE INCLUDE
IRREGULAR PIGMENTATION, ERUPTIVE NEVI,
ABNORMAL REGROWTH OF NAILS, AND
ALOPECIA
OPHTHALMOLOGIC COMPLICATIONS INCLUDE DRY
EYE, PHOTOPHOBIA, VISUAL IMPAIRMENT, AND
CORNEAL SCARRING THAT CAN LEAD TO
BLINDNESS
IT IS IMPERATIVE TO OBTAIN AN
OPHTHALMOLOGY CONSULTATION IN A
PATIENT WITH SJS TO PREVENT OCULAR
DAMAGE
GENITOURINARY COMPLICATIONS IN
WOMEN INCLUDE LABIAL AND VAGINAL
ABNORMALITIES AND URINARY RETENTION
LONG-TERM PULMONARY COMPLICATIONS
INCLUDE CHRONIC
BRONCHITIS/BRONCHIOLITIS, BRONCHIECTASIS,
AND OBSTRUCTIVE DISORDERS
BECAUSE THE MOST COMMON CAUSE OF SJS IS A
REACTION TO MEDICATION, THE MOST IMPORTANT FIRST
STEP IN TREATMENT IS TO STOP THE OFFENDING
MEDICATION
SJS IS FREQUENTLY TREATED IN BURN UNIT OR
INTENSIVE CARE UNIT WITH
CORTICOSTEROIDS, ANALGESICS, AND
INTRAVENOUS FLUIDS