Abetalipoproteinemia: decrease ApoB-48, Apo B-100; pigmentary degeneration of retina, acanthocytes, steatorrhea, cerebellar ataxia.
Acute Fatty Liver of Pregnancy: microvesicular steatosis in the liver, mitochondrial dysfunction in the oxidation of fatty acids leading to an accumulation in hepatocytes
Alkaptonuria: homogentisate oxidase deficiency, increase homogenistic acid, ochronosis, dark blue urine.
AcylCoA Dehydrogenase deficiency (MCAD): fasting hypoglycemia, no ketone bodies, dicarboxilic acidemia.
Bernard Soulier Sd: gp1b deficiency, prolonged bleeding time
Bloom Sd: chromosome 15, Ashkenazi Jews, BLM gene.
Carpenter Sd: craniosynostosis, acrocephaly, craniofacial asymmetry, increased ICP, cutaneous syndactyly, polydactily, mild-profound MR.
Chediak Higashi Sd: Lyst gene mutation, microtubule polymerization defect, no phagolysosome formation, albinism.
Chondrodystrophy: normal-sized trunk and abnormally short limbs and extremities (dwarfism)
Congenital Adrenal Hyperplasia: 17alpha or 21beta or 11 beta hydroxylase deficiency; enlargemente od adrenal glands due to increase ACTH
Congenital Hepatic Fibrosis: hepatic (periporta) fibrosis, irregularly shaped proliferating bile duct, portal hypertension, renal cystic disease.
Cystic Fibrosis: CFTR gene, Phe508, defective Chloride channel, chromosome 7.
Dubin-Johnson Sd: direct hyperBbnemia, cMOAT deficiency, black liver
Endocardial Fibroelastosis: restrictive/infiltrative cardiomyopathy, thick fibroelastic tissue in endocardium of young children, <2yo
Familial Mediterranean Fever: chromosome 16, recurrent autoinflammatory disease, characterized by F°, PMN disfx, sudden attacks pain/inflammation (7 types of attacks (abdominal, joints, chest, scrotal, myalgias, erysipeloid, fever). Complication: AA-amyloidosis
Fanconi Anemia: genetic loss of DNA crosslink repair, often progresses to AML, short stature, ↑incidence of tumors/leukemia, aplastic anemia
Friedreich’s Ataxia: GAA triplet repeat, chromosome 9, neuronal degeneration, progressive gait & limb ataxia, arreflexia, hypertrophic cardiomyopathy, axonal sensory neuropathy, kyphoscoliosis, dysarthria, hand clumsiness, loss of sense of position, impaired vibratory sensation.
Gaucher’s disease: glucocerebrosidase deficiency, glucocerebroside accumulation, femur necrosis, crumpled paper inclusions in macrophages.
Ganzman’s thromboasthenia: gpIIbIIIa deficiency, deficient platelet aggregation.
Hartnup Disease: tryptophan deficiency, leads to niacin deficiency, pellagra-like dermatosis
Hemochromatosis: HFE gene, C282Y MC mutation, chromosome 6, unrestricted reabsorption of Fe+ in SI, iron deposits in organs, bronze diabetes, DM1, malabsorption, cardiomyopathy, joint degeneration, increased iron, ferritin, TIBC. Complications: liver cirrhosis, hepatocelullar carcinoma
Homocystinuria: due to B6 deficiency (defective Cystathionine synthase) or due to B9,B12 deficiency (defective Homocysteine Methyltrasnferase), dislocated lenses (in & down), DVT, stroke, atherosclerosis, MR.
Krabbe's Disease: Galactocerebrosidase deficiency, galactocerebroside accumulation, gobloid cells, optic atrophy, peripheral neuropathy.
Leukocyte Adhesion Defect (LAD): CD-18+ deficiency, omphalitis in newborns, chronic recurrent bacterial infxs, increase WBC count, no abscess or pus formation.
Metachromic Leukodystrophy: Aryl-sulfatase A deficiency, sulfatides accumulation, Demyelination (central & peripheral), Ataxia, Demantia (DAD)
Niemann-Pick Disease: sphingomyelinase deficiency, sphingomyelin accumulation, HSM, cherry-red macula, foam cells.
Phenylketonuria (PKU): phenylalanine hydroxylase deficiency, Phe accumulation, MR, microcephaly, diet low in Phe!!! also in pregnancy, avoid aspartame, musty odor.
Polycystic Kidney Disease (children): ARPKD, rogressive & fatal renal failure, multiple enlarged cysts perpendicualr to renal capsule, association with liver cysts. Bilateral palpable mass.
Rotor Sd: direct hyperBbnemia, cMOAT deficiency, no black liver
Shwaman Diamond Sd: exocrine pancreatic insufficiency (2°MCC in children after CF), bone marrow dysfunction, skeletal abnormalities, short stature.
Situs inversus: assoc w/ Kartagener sd
Sicke Cell Disease and Trait: Hb S, beta globin chain, chromosome 11, position 6, nucleotide codon change (glutamic acid --> valine), vaso-occlusive crisis (pain), autosplenectomy, acute chest pain sd, priapism, hand-foot sd, leg ulcers, aplastic crisis, drepanocytes & Howell-Jolly bodies, hemolytic anemia, jaundice, bone marrow hyperplasia
Tay-Sachs Disease: Hexoaminidase A deficiency, GM2 accumulation, cherry-red macula, onion skin lysosomes.
Thalasemia: alpha (chromosome 16, gene deletion), beta (chromosome 11, point mutation)
Werner Disease: adult progeria
Wilson’s Disease: Chromosome 13, WD gene, ATP7B gene (encondes for Copper transporting ATPase), copper accumulation in liver, brain (putamen), eyes (Descemet membrane - Kayser-Fleischer ring), decreased ceruloplasmin.
Xeroderma Pigmentosa: defective excision endonuclease, no repair of thymine dymers caused by UV radiation, excessive freckling, multiple skin cancers.
Most Common Site of Primary Bone Tumors
- Chondroblastoma (before physeal closure)
- Osteoclastom/Giant cell tumor (after physeal closure in adults)
- Articular osteochondroma
- Bone cyst
- Osteoclastoma (in children)
- Osteomyelitis mostly starts in metaphysis
- Round cell lesions: Ewing’s sarcoma/Multiple myeloma /Reticulum cell sarcoma
- Osteoid osteoma
- Ankylosing spondylitis or AS, is a form of arthritis that primarily affects the spine, although other joints can become involved.
- It causes inflammation of the spinal joints (vertebrae) that can lead to severe, chronic pain and discomfort.
- Most people with AS have an antigen called HLA-B27
- Ankylosing spondylitis (AS) is a chronic, multisystem inflammatory disorder involving primarily the sacroiliac joints and the axial skeleton.
Key components of the patient history that suggest AS include the following:
• Insidious onset of low back pain - The most common symptom
• Onset of symptoms before age 40 years
• Presence of symptoms for more than 3 months
• Symptoms worse in the morning or with inactivity
• Improvement of symptoms with exercise
- AS can cause pain and inflammation in other parts of your body.
- Eyes. About 40% of people with AS have an eye problem called uveitis. It’s a painful inflammation that can blur your vision and make you sensitive to bright light.
- Heart valve. It’s not common, but AS can enlarge the aorta, the largest artery in your body. This can change the shape of the aortic valve, which can allow blood to leak back into your heart.
- Cancer. A large study found that people with AS are more likely to get certain types of cancers. They include bone and prostate cancers in men and colon cancer in women, as well as blood-related cancers in both sexes.
Thalassemias are a heterogeneous group of hereditary blood disorders characterized by faulty globin chain synthesis resulting in defective hemoglobin, which can lead to anemia
Thalassemia provides partial resistance against malaria.
Minor variant (heterozygous): unremarkable symptoms (low risk of hemolysis, rarely splenomegaly)
Major variant (homozygous) Severe hemolytic anemia, Hepatosplenomegaly ,Growth retardation ,Skeletal deformities (high forehead, prominent zygomatic bones, and maxilla)
most commonly seen in people of Asian and African descent
Silent carrier: asymptomatic
Alpha thalassemia trait: mild hemolytic anemia with normal RBC and RDW
Hemoglobin H disease
Jaundice and anemia at birth
Chronic hemolytic anemia which may require transfusions
Hb-Bart's hydrops fetalis syndrome (most severe variant of alpha thalassemia)
Intrauterine ascites and hydrops fetalis, severe hepatosplenomegaly, and often cardiac and skeletal anomalies
Incompatible with life (death in utero or shortly after birth)
Microcytic hypochromic anemia
Blood smear: target cells , teardrop cells
Bone marrow biopsy: reactive hyperplasia
Hb-electrophoresis Alpha thalassemia can usually only be detected if ≥ 3 alleles are defective.
DNA analysis: to test for alpha thalassemia minor and minima (< 3 alleles defective)
Skeletal deformities -high forehead, prominent zygomatic bones and maxilla can be seen on all imaging modalities.
X-ray: hair-on-end (“crew cut”) sign
• Thoracic empyema is purulent pleural effusion
• End stage of pleural effusion if not treated properly
• Thick pus with a thick cortex of fibrin and coagulum over lung
Most common cause : Parapneumonic, Postsurgical & post-traumatic
Most common: pneumonia → extension of bacterial infection into the pleural space
Less common: infected hemothorax, ruptured lung abscess, esophageal tear, thoracic trauma
Empyema due to pneumonia three phase
The exudative phase :
- protein > 3g/100 ml
- Infection from lung
- Antibiotics & aspiration or drainage
The fibrinopurulent phase :(next few days)
Pleural fluid become thick ,
The organized phase:
- Lung trapped by thick peel or cortex
- Surgical management
Condition predispose to Empyema
- Unresolved pneumonia
- Fungal infection
- Lung abscess
Aspiration of pleural effusion
- Penetrating injury
- Oesophgeal peforation
Extrapulmonary sources : Subphernic abscess
Bone infection osteomyelitits ribs and vertebra
- Caused by fungal organism called Pneumocystis jiroveci. Previously known as Pneumocystis carinii (PCP).
- Causes a pneumonia in the immunosuppressed, typically HIV with CD4 <200 therefore may require prophylaxis. Also seen in lymphoproliferative disorders, organ transplants and chemotherapy patients.
- Insidious onset, increasing dyspnoea, dry cough and fever. Patient may have bilateral fine crepitations and signs of hypoxia.
- CXR - can be normal, or classically showing bilateral perihilar interstitial shadowing. The CXR above also shows cavitating lesions.
- CT - ground glass appearance. This CT shows multiple cavitations.
- Diagnosis - direct visualisation on microscopy specimen from bronchoalveolar lavage or biopsy.
- Management - ASAP give high dose IV co-trimoxazole or IV penamidine. Steroids useful in severe hypoxia. Supportive therapy with oxygen. May require CPAP or mechanical ventilation.
- Complication of open abdominal surgery, especially when the bowel is frequently manipulated, with possible disruption of bowel anastomosis, inadvertent enterotomy, or small bowel injury.
- Can occur as early as 8 days from initial laparotomy
- Other causes: cancer, irradiation, IBD
Enterocutaneous fistula: abnormal communication between the small or large bowel and the skin
Subtype enteroatmospheric fistula: abnormal communication between GI tract and the atmosphere, associated with high morbidity and mortality
Complications: sepsis, fluid and electrolyte abnormalities, malnutrition
Conservative treatment and electrolyte repletion, antibiotics (in case of infections), nutritional support, control of fistula drainage (e.g., ostomy pouch), skin protection
Spontaneous closure occurs in roughly 70% of patients
Surgical Treatment : attempted 1–4 months after trial of conservative therapy if no signs of spontaneous closure
Lysis of adhesions
Resection of abnormal or diseased bowel
Reanastamosis of healthy bowel
The proliferation and functioning of endometrial tissue outside of the uterine cavity
Incidence: - 15-30% of all premenopausal women, -mean age at presentation: 25-30 years
Etiology - unknown
- retrograde menstruation theory of Sampson
- Mullerian metaplasia theory of Meyer
- endometriosis results from the metaplastic transformation of peritoneal mesothelium under the influence of certain unidentified stimuli
- lymphatic spread theory of Halban
- surgical transplantation
- deficiency of immune surveillance
- age > 25 years
- family history
- obstructive anomalies of genital tract
Sites of Occurrence
ovaries most common location, 60% of patients have ovarian involvement
peritoneal surface of the cul-de-sac (uterosacral ligaments)
there may be little correlation between the extent of disease and symptomatology
pelvic pain - due to swelling and bleeding of ectopic endometrium, unilateral if due to endometrioma
dysmenorrhea (secondary) - worsens with age, suprapubic and back pain often precede menstrual flow (24-48 hours) and continue throughout and after flow
infertility - 30-40% of patients with endometriosis will be infertile, 15-30% of those who are infertile will have endometriosis
dyspareunia on deep penetration
premenstrual and postmenstrual spotting
bladder symptoms - frequency, dysuria, hematuria
bowel symptoms - direct and indirect involvement diarrhea, constipation, pain and hematochezia
truly a surgical diagnosis
history - cyclic symptoms - pelvic pain, dysmenorrhea, dyschezia
- tender nodularity of uterine ligaments and cul-de-sac
- fixed retroversion of uterus
- firm, fixed adnexal mass (endometrioma)
- dark blue or brownish-black implants (mulberry spots) on the uterosacral ligaments, cul-de-sac, or anywhere in the pelvis
- chocolate cysts in the ovaries (endometrioma)
- powder-burn lesions
- early white lesions and blebs
pseudopregnancy - cyclic estrogen-progesterone (OCP) or medroxyprogesterone (Provera)
pseudomenopause - danazol (Danocrine) = weak androgen, s/e: weight gain, fluid retention, acne, or hirsutism, leuprolide (Lupron) = GnRH agonist (suppresses pituitary GnRH)
s/e: hot flashes, vaginal dryness, reduced libido, and osteoporosis with prolonged use .these can only be used short term because of osteoporotic potential
- laparoscopic resection and lasering of implants
- lysis of adhesions
- use of electrocautery
- unilateral salpingo-oophorectomy
- uterine suspension
- rarely total pelvic clean-out
- follow-up with 3 months of medical treatment
Each cavernous sinus is a large venous space situated in the middle cranial fossa on either side of the body of the sphenoid bone. Its interior is divided into a number of trabeculae or caverns. The floor of the sinus is formed by the endosteal dura mater. The lateral wall, roof and medial wall are formed by the meningeal dura mater.
Structures in the lateral wall of the sinus from above downwards:
Structures passing through the centre of the sinus:
Tributaries (incoming channels) of cavernous sinus
Draining channels (communications) of cavernous sinus
- Works on Cyclo-oxygenase (AA -> thromboxane)
- Low dose (80-160 mg/day) irreversibly inhibits plt COX, and they can’t make new COX b/c they have no nucleus
- Some inhibition of endothelial COX but not much, therefore prostacyclin (anti-coag) synthesis isn’t affected much
- Benefit is greater after thrombolysis
- SE is bleeding
- Prophylaxis for MI or TIA (80mg/day), higher doses for post-MI/TIA (160-325mg/day)
- Contraindications (bleeding risk): Vit. K def., Hemophilia, Hypoprothombinemia, pregnancy & childbirth
- ADP antagonist
- Competes with ADP for P2Y receptor (prevents lowering of cAMP)
- Less incidence of neutropenia/thrombocytopenia
- Used in combo with ASA
- ADP antagonist, prodrug
- Often used in combo with ASA (synergistic)
- May cause severe neutropenia (1%)
- phosphodiesterase inhibitor (prevents cAMP breakdown)
- Eptifibatide, Abciximab, Tirofiban
- Block the receptor for fibrinogen blocking plt Aggregation
Heparin (& derivatives)
- Stimulates natural anticoags (antithrombin)
- Monitor using aPTT (add negative charges)
- Negatively charged, therefore cannot cross membranes (given IM, IV, parentally)
- Good for pregnancy
- Eliminated by RES & macrophages
- Potentiates AT III (in the plasma) – inhibits IIa, Xa, IXa and VIIa
- Toxicity – hemorrhage
- Antidote – protamine sulfate (1mg for every 100 units of heparin)
Heparin-Induced Thrombocytopenia (HIT) – occurs 5-10 days after, stop heparin immediately; use alternatives lepirudin/danaparoid
- Good for PE and DVT and during pregnancy
LMWH – better bioavailability, can be given subcut. w/o lab monitoring as outpatient, less risk of bleeding
- More expensive, not good in renal failure, not for pregnancy
- DOES NOT inhibit IIa (but inhibit Xa)
- Good for DVT, PE and UA
Danaparoid – promotes inhibition of Xa by AT (for HIT)
Lepirudin – direct thrombin inhibitor (for HIT)
Coumarin (Oral) anticoags
- Monitored using PT (add tissue factor)
- Inhibit Vit. K Epoxide reductase in liver
-Prevents carboxylation of Vit.K dependent factors
-Takes 4-5 days to get effective (carboxylated fx’s in plasma need to be cleared before inactive ones take over)
-Small volume of distribution, steep dose-response curve (small therapeutic window)
- For DVT and PE, prosthetic heart valves or Afib, MI
-Metabolized by CYP1A and CYP2C9
-Efficacy measured by INR, pt’s PT time divided by PT time in pooled plasma
- INR = (PTpt/PTref)^ISI (target is 2.0 – 3.0)
- Warfarin overdose
- Give Excess Vit.K, goes through a diff enzyme that isn’t inhibited by warfarin (Diaphorase)
Fibrinolytics (lyse formed thrombi)
Streptokinase – turns plasminogen -> plasmin
-Plasmin breaks down fibrin (lysis of formed clot) Dissolves clots post-MI/DVT/PE
- SE – bleeding (systemic plasminogen activation), allergy, hTN, fever
- Streptokinase has an additive effect with ASA
Tissue plasminogen activator (tPA) – acts on fibrin and circulating plasminogen -> plasmin
- Less systemic plasmin
- Same indications as streptokinase
- More expensive