Huntington’s Chorea

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Huntington’s Disease is caused by a gene mutation that creates excess copies of the CAG codon which genetically program the degeneration of the neurons of the brain.It is an Autosomal Dominant disease.The cells of the basal ganglia, caudate nucleus and cortex of the brain are specifically targeted in HD.
The number of CAG codons varies and so does the severity of the disease
Age of onset varies based on the number of repeats.
The earliest onset of Huntington’s ever documented was a two year old boy who was found to have nearly 100 CAG repeats.
The symptoms of HD can also develop at 55 or later, in which case it is harder to recognize.

What is Juvenile Huntington’s Disease?
10% of Huntington’s cases.
Usually 80-100 CAG repeats
stiffness or rigidity in joints as opposed to chorea for adult-onset HD
1/3 of Juvenile HD patients have recurring seizures.
Believed to inherit large numbers of repeats from father.

How is Huntington’s Disease Diagnosed?
Symptoms are frequently recognized by people who have history with the disease, but for others there is testing.
Huntington’s can be diagnosed by a simple blood test at any age.
There are three types of tests that can be taken to determine an HD diagnosis:
Prenatal testing
Pre-symptomatic testing
Confirmatory testing

Neuropathology
The symptoms are caused by a loss of neurons in the brain that occurs about the time that disease becomes first manifest
The basal ganglia and cortex are ravaged, which can be followed up with a MRI or PET
In the caudate nucleus, populations of enkephalin and substance P containing medium-sized spiny GABAergic projection neurons are the first to be affected
The exhibit wilted and recurved dendritic endings and changes in the density, shape and size of the spines.
The large acetylcholine rich or smaller somatostatin and neuropeptide Y containing aspiny interneurons are spared by the disease process
It is this characteristic pattern of neuronal cell loss in the basal ganglia that forms the basis for the neurophathological grading of HD

Adhesive Capsulitis (Frozen Shoulder)A disorder in which the shoulder capsule becomes inflamed and stiff, greatly restricting motion and causing pain.
The etiology is unknown (injury or trauma, autoimmune).
Characterized by progressive pain and stiffness which usually resolves spontaneously after 18 months.
Movement of the shoulder is severely restricted, pain is worse at night.

Clinical Features
Age 40-60, more in females
Slight wasting, some tenderness.
Pain (gradual onset)
Stiffness or decrease in motion.
External rotation (most severely inhibited)
Internal rotation
Abduction.

Radiology
X-ray:
Osteoporosis of the proximal humerus (decreased bone density)
Arthrography:
Shows a contracted joint
Dramatic decrease in the injected contrast material.
Loss of normally loose dependent folds of the capsule.

Differential Diagnosis
Post-traumatic stiffness (maximal at the start, gradually lessens)
Disuse stiffness
Regional pain syndrome (associated with MI, stroke)

Treatment
self-limiting: it usually resolves over time without surgery. Movement is regained gradually but may not return to normal
Conservative:
Analgesics
Heat therapy and exercise(physiotherapy)
Corticosteroid injection.
Manipulation under anesthesia hastens recovery.

Operative Treatment
Arthroscopic division of the interval between supraspinatous and infraspinatous (improve the range of movement).

Shoulder Instability (Dislocation)
Occurs when the humerus separates from the scapula at the glenohumeral joint. The glenoid socket is very shallow and the joint is held secure by the fibrocartilaginous glenoid (labrum) and the surrounding ligaments and muscles.
Types
Anterior instability.
Posterior instability.
Multidirectional instability.

Treatment

Reduction:
Most techniques are facilitated by the following 2 maneuvers:
Flexion of the elbow 90° to relax the biceps tendon
External rotation of the humerus, which releases the superior glenohumeral ligament and presents the favorable side of the humeral head to the glenoid fossa
Signs of a successful reduction include the following:
Palpable or audible clunk
Return of rounded shoulder contour
Relief of pain
Increase in range of motion

Stimson Maneuver, Scapular Manipulation, External rotation method, Traction and counter traction

Causes of Pituitary Masses
Evaluation of a Pituitary Incidentaloma
Management of Pituitary Neoplasia
Abnormal Anterior Pituitary Function Associated with Pituitary Masses
Hyperprolactinemia and Prolactinomas

Etiology of Pituitary-Hypothalamic Lesions
Non-Functioning Pituitary Adenomas
Endocrine active pituitary adenomas
Prolactinoma
Somatotropinoma
Corticotropinoma
Thyrotropinoma
Other mixed endocrine active adenomas
Malignant pituitary tumors: Functional and non-functional pituitary carcinoma
Metastases in the pituitary (breast, lung, stomach, kidney)
Pituitary cysts: Rathke's cleft cyst, Mucocoeles, Others
Empty sella syndrome
Developmental abnormalities: Craniopharyngioma (occasionally intrasellar location), Germinoma, Others
Primary Tumors of the central nervous system: Perisellar meningioma, Optic glioma, Others
Vascular tumors: Hemangioblastoma, Others
Malignant systemic diseases: Hodgkin's disease, Non-Hodgkin lymphoma, Leukemic infiltration, Histiocystosis X, Eosinophilic granuloma, Giant cell granuloma (tumor)
Granulomatous diseases: Neurosarcoidosis, Wegner's granulomatosis, Tuberculosis, Syphilis
Vascular aneurysms (intrasellar location)

Radiologic Evaluation: MRI
Preferred imaging study for the pituitary
Better visualization of soft tissues and vascular structures than CT
No exposure to ionizing radiation
Images are generated based upon the magnetic properties of the hydrogen atoms
T1-weighted images produce high–signal intensity images of fat. Structures such as fatty marrow and orbital fat show up as bright images.
T2-weighted images produce high-intensity signals of structures with high water content, such as cerebrospinal fluid and cystic lesions

Radiologic Evaluation: CT
Better at visualizing bony structures and calcifications within soft tissues
Better at determining diagnosis of tumors with calcification, such as germinomas, craniopharyngiomas, and meningiomas
May be useful when MRI is contraindicated, such as in patients with pacemakers or metallic implants in the brain or eyes
Disadvantages include:
less optimal soft tissue imaging compared to MRI
use of intravenous contrast media
exposure to radiation

Clinical Evaluation
All patients with macroadenomas should have formal visual field testing
In addition to radiographic and hormonal evaluation, patients should be asked and examined for any clinical signs suspicious for pituitary hyperfunction or hypofunction.

Hormonal Evaluation
May include of both basal hormone measurement and dynamic stimulation testing.

All pituitary masses should have screening basal hormone measurements, including:
Prolactin
TSH, FT4
ACTH, AM cortisol, midnight salivary cortisol
LH, FSH, estradiol or testosterone
Insulin-like growth factor-1 (IGF-1)

Dynamic stimulation/suppression testing may be useful in select cases to further evaluate pituitary reserve and/or for pituitary hyperfunction
  • Dexamethasone suppression testing
  • Oral glucose GH suppression test
  • GHRH, L-dopa, arginine
  • CRH stimulation
  • Metyrapone
  • TRH stimulation
  • GnRH stimulation
  • Insulin-induced hypoglycemia


DNA testing for Down syndrome

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Down syndrome is the Commonest genetic cause of intellectual disability worldwide.
Increased risk with advancing maternal age.
Cause
Non-disjunction / trisomy        95%
Translocation                          4%
  About 50% de novo
Mosaicism                              1%

Clinical features
Craniofacial
Brachycephaly, upslanted eyes, epicanthic folds, flat facial profile, flat nasal bridge, (protruding tongue), (dysplastic ears)
Limbs
Brachydactyly, single palmar crease, clinodactyly, sandle-gap
Cardiac (40%)
ASD, VSD, AVSD, PDA
CNS
Hypotonia, developmental delay, MR
Other
GIT abnormalities (~15%), short stature

Complications
Atlanto-axial instability
Transient neonatal ‘leukaemia’
ALL (20 X greater risk)
Hypothyroidism (antibodies) in 30%
Alzheimer disease

Quantitative fluorescent PCR aneuploidy screen (QF-PCR)
Principle:
Test STR markers on chromosomes
 4-5 on autosomes of choice (13, 18, 21)
 Fewer on X and Y
Used to detect numerical chromosome abnormalities
Can test blood, amniotic fluid, CVS, post-mortem tissue etc...

Vasculitis syndromes

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Kawasaki Syndrome(Mucocutaneous lymph node syndrome)
Diagnostic criteria:
 Fever for > 5 days plus 4 of the following:
 Bilateral bulbar conjunctival injection
 Mucous membrane changes (injected pharynx, cracked lips, strawberry tongue)
 Extremity changes (edema, erythema, or desquamation of hands or feet)
 Polymorphous rash
 Cervical lymphadenopathy (at least one >1.5 cm)

Clinical manifestions
Arthritis and arthralgia
  Present in 7-25% of patients
  Involves large or small joints
Urethritis
  Causes sterile pyuria
CNS involvement
  Aseptic meningitis, facial nerve palsy, hearing loss
GI symptoms
  Abdominal pain, diarrhea, vomiting, hepatitis
Cardiac involvement
Coronary artery aneurysms, myocardial dysfunction

Henoch-Schonlein Purpura
Most common systemic vasculitis in children.
Immune mediated
 Deposition of IgA immune complexes.
Often a self-limited disease.
Occurs more often in fall, winter, and spring.
 Rare in the summer.
About 50% of cases are preceded by URI’s.
 Streptococcus is often implicated.
 Vaccines, insect bites, viruses have also been reported as triggers.

Classic tetrad
Palpable purpura (100%)
In absence of thrombocytopenia or coagulopathy
Arthritis or arthralgia (75%)
Abdominal pain (50%)
Renal disease (21-50%)

Behçet Disease
Very rare systemic vasculitis of unknown etiology.
Affects blood vessels of all sizes.
 Both arteries and veins
Clinical manifestations are similar in children and adults.
Characterized by recurrent, painful ulcers of the mouth and skin and uveitis.

Clinical Presentation
Apthous stomatitis
Genital ulcerations
Uveitis
GI symptoms (due to ulcers)
Arthritis
Lab findings
 Normal ANA and RF
 ESR/CRP may be elevated

Scleroderma
Juvenile Systemic Sclerosis
Characterized by symmetrical fibrous thickening of skin and various internal organs.
 Esophagus and GI tract, heart, lungs, kidneys
Clinical presentation
 Skin changes – edema then tightening, thinning, atrophy
 Raynaud’s – 70% at presentation
 Arthritis, arthralgia
 Muscle weakness/pain
 CREST syndrome
Pulmonary fibrosis and pulmonary hypertension are major causes of morbidity in children.

Wound healing

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Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury.In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment. Once the protective barrier is broken, physiologic process of wound healing is immediately set in motion. The classic model of wound healing is divided into three or four sequential, yet overlapping,phases:hemostasis, inflammatory,proliferative and remodeling.Upon injury to the skin, a set of complex biochemical events takes place in a closely orchestrated cascade to repair the damage.Within minutes post-injury, platelets  aggregate at the injury site to form a fibrin clot. This clot acts to control active bleeding.
In the inflammatory phase, bacteria and debris are phagocytosed and removed, and factors are released that cause the migration and division of cells involved in the proliferative phase.
The proliferative phase is characterized by angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction.In angiogenesis, new blood vessels are formed by vascular endothelial cells.In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin.Concurrently, re-epithelialization of the epidermis occurs, in which epithelial cells proliferate and 'crawl' atop the wound bed, providing cover for the new tissue.
In contraction, the wound is made smaller by the action of myofibroblasts, which establish a grip on the wound edges and contract themselves using a mechanism similar to that in smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis.
In the maturation and remodeling phase, collagen is remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosis.

Antiphospholipid Antibody Syndrome

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Most common acquired thrombophilia
A syndrome characterized by the association of:
thrombosis, obstetric complications and/or thrombocytopenia
antibodies against phospholipids or against proteins bound to phospholipids.
Combination of genetic background and environmental factors: infection, trauma, drugs

Antiphospholipid Antibodies
10% of healthy donors, 30-50% of SLE patients
LA antibodies are directed against plasma proteins bound to anionic phospholipids
aCL antibodies are directed against phospholipids bound to proteins
 Can be IgA, M, or G (subclasses 1-4)
 IgG (esp G2) associated with a greater risk of APS
Anti b2GPI antibodies are directed against a plasma protein that binds phospholipid with high affinity

Lupus Anticoagulant (LA) Antibodies
 Prolonged coagulation in phospholipid-dependent in vitro tests (aPTT, PT, dRVVT)
 Failure to correct with 50:50 mix
 Correction of coagulation time by adding phospholipid
Anticardiolipin (aCL) Antibodies
 ELISA assay in the presence of bovine B2GPI
Anti-Beta 2 Glycoprotein I Antibodies (b2GPI)
 ELISA assay using human B2GPI coated plates
 most specific

Diagnosis - Clinical Criteria
Vascular thrombosis: arterial, venous, or small vessel, in any tissue or organ, confirmed by objective validated criteria
Pregnancy morbidity:
- Unexplained fetal death at or beyond 10 weeks gestation
- Premature birth before 34 weeks gestation because of
eclampsia, severe pre-eclampsia, or placental insufficiency
- Three or more consecutive spontaneous abortions before
10 weeks gestation

Diagnosis - Laboratory criteria
Lupus anticoagulant, present on at least 2 occasions, at
least 12 weeks apart
Anticardiolipin antibodies (ACA), IgG or IgM >30 units for both, present on at least 2 occasions, at least 12 weeks
apart
Anti-beta-2-glycoprotein I antibodies (anti-B2GPI), IgG or IgM >20 units for both, present on at least 2 occasions, at least 12 wks apart

A diagnosis of APS should not be made if a period of greater
than five years separates the clinical event and positive
laboratory test.

Catastrophic APS
Preliminary criteria:
1. Involvement of three or more organs or tissues
2. Development of manifestations simultaneously or in < 1 week 3. Histopathologic evidence of small-vessel occlusion in at least one type of tissue 4. Presence of lupus anticoagulant, anticardiolipin antibodies or both Definite diagnosis: All four criteria met Probable diagnosis: 2 organs or tissues involved, and the 2nd, 3rd and 4th criteria met; or All 4 criteria met and negative test for LA or anticardiolipin antibody > 6
wks after the first positive test or death within that period; or
First, 2nd and 4th criteria met; or
First, 3rd and 4th criteria met and development of a third manifestation
in >1 wk but <1 mo despite anticoagulation


Symptoms and signs of pregnancy

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Early Symptoms
Secondary amenorrhea
Breast symptoms - Mastalgia heaviness,pain,pigmentation
Bladder symptoms - Freaquency
General symptoms - Dizziness,palpitation,dyspnoea,syncopal attacks
GIT symptoms -Nausea and Vomiting,Ptyalism: excessive salivation,Heart burn ,Eructation ,Indigestion,Distension,Constipation
Psychological symptoms - Irritability,Suicidal attempts,Crying ,Depression,longing

Late Symptoms
Abdominal enlargement
Quickening
Braxton-hicks contractions
Increased intra-abdominal pressure

Signs on the abdomen
  • Abdominal enlargement
  • Striae Gravidarum
  • Linea nigra
  • Fetal movements
  • Braxton-Hicks
  • Foetal heart sounds
  • Flat umbilicus
  • External ballottement


Fanconi Anemia

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What is Fanconi Anemia?
Fanconi Anemia is an autosomal recessive disorder.
We all have FA genes.
Known mutations involved:  FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, and FANCM
Fanconi Anemia predisposes an individual to numerous types of cancer, including acute myeloid leukemia, breast cancer, squamous cell carcinoma of the head and neck, and cancers of the gynecological system, skin, esophagus, liver, and kidney

Common presentations of patients with Fanconi Anemia:
Anemia
Pancytopenia
Bone marrow hypoplasia
Thrombocytopenia
Low Birth Weight
Short stature
Absence of or malformity in hands and arms, for example the absence of a thumb or the presence of polydactyly
Presence of only one kidney or of a horseshoe kidney

Gene therapy to target this role of FA genes in individuals with FA gene mutations.

Diagnosis
DEB and MMC tests
Diagnosis typically occurs before the age of twelve (Fanconi Anemia Research Fund, Inc., 2006).
MMC test is used to diagnose Fanconi Anemia at the University of Kentucky.
Subtyping via use of retroviruses needs to be incorporated into standard protocol when diagnosing a patient with Fanconi Anemia.

Treatment
Retrovirus mediated gene transfer
Lentivirus mediated gene transfer

Risks of Gene Therapy
Retrovirus potential to stimulate oncogenes.
Lentivirus association with arthritis and encephalitis in goats, leukemia in cattle, anemia in horses, and immunodeficiency

Femoral Head Fractures

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Femoral Head Fractures – Mechanism
Fracture occurs by shear as femoral head dislocates.
With less hip flexion, femoral head fracture tends to be larger.

Classification
Thomas and Epstein Type V
  Hip dislocation with femoral head fracture

Pipkin Classification
I Fracture inferior to fovea
II Fracture superior to fovea
III Fracture of femoral head with fracture of femoral neck
IV Fracture of femoral head with acetabulum fracture

Femoral Head Fracture - Radiographic Evaluation
AP Pelvis X-Ray
Lateral Hip X-Ray
Judet views
Post-reduction CT Scan

Displaced Infra-foveal Fractures
Can be reduced and stabilized, or excised.
ORIF preferred if possible.
Anterior approach allows best visualization.

Supra-foveal Fractures
ORIF through:
    anterior approach.
    posterior approach.
    posterior approach with Ganz     trochanteric flip osteotomy.
Excision of fragment(s) will create instability, and thus is contraindicated.

Pipkin III Fractures
High incidence of AVN with displaced fractures.
Relative indication for hemiarthroplasty in older patient.
If femoral head fracture is non-displaced, do not attempt manipulative reduction of hip until femoral neck is stabilized.

Fracture-Dislocation with Displaced Femoral Neck Fracture
Closed reduction attempts are futile.
ORIF in young: open reduction of hip, then reduction and stabilization of femoral neck and head.
Arthroplasty in middle-aged and elderly (No good results with ORIF reported in literature)....

Hip Dislocations

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Hip dislocations caused by significant force:
Association with other fractures
Damage to vascular supply to femoral head
Thus, high chance of complications

Anatomy of the Hip Joint
Ball and socket joint.
Femoral head: slightly asymmetric, forms 2/3 sphere.
Acetabulum: inverted “U” shaped articular surface.
Ligamentum teres, with artery to femoral head, passes through middle of inverted “U”.

Joint Contact Area
Throughout ROM:
 40% of femoral head is in contact with acetabular articular cartilage.
 10% of femoral head is in contact with labrum.
Acetabular Labrum
Strong fibrous ring
Increases femoral head coverage
Contributes to hip joint stability

Hip Joint Capsule
Extends from intertrochanteric ridge of proximal femur to bony perimeter of acetabulum
Has several thick bands of fibrous tissue
    Iliofemoral ligament
Upside-down “Y”
Blocks hip extension
Allows muscle relaxation with standing

Blood Supply to Femoral Head
1.Artery of Ligamentum Teres
Most important in children.
Its contribution decreases with age, and is probably insignificant in elderly patients.

2. Ascending Cervical Branches
Arise from ring at base of neck.
Ring is formed by branches of medial and lateral circumflex femoral arteries.
Penetrate capsule near its femoral attachment and ascend along neck.
Perforate bone just distal to articular cartilage.
Highly susceptible to injury with hip dislocation.

Hip Dislocation: Mechanism of Injury
Almost always due to high-energy trauma.
Most commonly involve unrestrained occupants in MVAs.
Can also occur in pedestrian-MVAs, falls from heights, industrial accidents and sporting injuries.

Posterior Dislocation
Generally results from axial load applied to femur, while hip is flexed.
Most commonly caused by impact of dashboard on knee.

Mechanism of Anterior Dislocation
Extreme abduction with external rotation of hip.
Anterior hip capsule is torn or avulsed.
Femoral head is levered out anteriorly.

Effect of Dislocation on Femoral Head Circulation
When capsule tears, ascending cervical branches are torn or stretched.
Artery of ligamentum teres is torn.
Some ascending cervical branches may remain kinked or compressed until the hip is reduced.
Thus, early reduction of the dislocated hip can improve blood flow to femoral head...

Major Mediators of Calcium and Phosphate Balance
Parathyroid hormone (PTH)
Calcitriol (active form of vitamin D3)

Role of PTH
Stimulates renal reabsorption of calcium
Inhibits renal reabsorption of phosphate
Stimulates bone resorption
Inhibits bone formation and mineralization
Stimulates synthesis of calcitriol

Role of Calcitriol
Stimulates GI absorption of both calcium and phosphate
Stimulates renal reabsorption of both calcium and phosphate
Stimulates bone resorption

Increased GI Absorption
    Milk-alkali syndrome
    Elevated calcitriol
        Vitamin D excess
            Excessive dietary intake
            Granuomatous diseases
        Elevated PTH
        Hypophosphatemia
Increased Loss From Bone
    Increased net bone resorption
        Elevated PTH
            Hyperparathyroidism
        Malignancy
            Osteolytic metastases
            PTHrP secreting tumor
    Increased bone turnover
        Paget’s disease of bone
        Hyperthyroidism
Decreased Bone Mineralization
    Elevated PTH
    Aluminum toxicity
Decreased Urinary Excretion
    Thiazide diuretics
    Elevated calcitriol
    Elevated PTH

Etiologies of Hyperphosphatemia
Increased GI Intake
    Fleet’s Phospho-Soda
Decreased Urinary Excretion
    Renal Failure
    Low PTH (hypoparathyroidism)
        s/p thyroidectomy
        s/p I131 treatment for Graves disease of thyroid cancer
        Autoimmune hypoparathyroidism
Cell Lysis
    Rhabdomyolysis
    Tumor lysis syndrome

Post Partum Complications

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Bleeding of 500 mL or more following delivery
Traditional definition vs. “new” definition:
Traditional:
 NVD => 500cc
 C-section => 1000cc
“New” criteria:
 Decreased Hct of 10 points OR
 The need for fluid replacement after birth

Early Post-Partum Hemorrhage
Hemorrhage occurs during first 24 hours after delivery
>500cc of blood loss
Caused by:
 retained fragments of placenta
 UTERINE ATONY 
  80-90% of the cases
 Blood may be expelled or retained in the vagina
 perineal injuries/lacerations
 inversion of uterus
 Episiotomy
 Hematomas: vulvar, vaginal, subperitoneal
 Coagulation disorders (i.e. hemophilia, thalassemia)

Most Common Causes of Hemorrhage
Residual placenta
Bleeding from placenta accreata – parts of the placenta adhers to the endometrium, in this case the chorionic villi attaches directly to the myometrium of the uterus (accounts for 80% of adherent placenta to the endometrium)
Placenta accreata may cause:
Maternal hemorrhage
Failure of the placenta to separate
Less common to bleed from placenta increta or placenta percreta (other placenta adherences)
Abdominal hysterectomy may be necessary, depending on involvement
Retained placenta: Surgical removal (D&C)

Late Post-Partum Hemorrhage
Hemorrhage occurs after the first 24 hours following delivery
Usually within 1-2 weeks after childbirth

Etiology: Late PP Hemorrhage
Subinvolution of the placenta site (due to):
Retained placental fragments
Signs of subinvolution:
Fundal height is greater than expected
Makes sure the woman ambulates and empties bladder
Lochia rubra fails to progress from        
 RUBRA----SEROSA----ALBA
Lochia rubra that persists > 2 weeks PP is highly suggestive of subinvolution

Post-Partum infection
Any infection of the reproductive organs that occurs within 28 days of delivery or abortion
Categories of Infections:
Puerperal infection: overall category
An infection of the reproductive tract associated with childbirth that occurs up to 6 weeks PP
1)  Endometritis or metritis
2)  Pelvic cellulites / Parametritis
3)  Peritonitis
4)  Salpinitis

Derived from the characteristic histologic changes by linght microscopyMesangiocapillary or lobular glomerulonephritis
Form of glomerulonephritis (inflammatory changes of glomerular capillaries) caused by an abnormal immune response with deposits of immune complex. Certain cells in the capillary wall (mesangial cells) increase in number and the parts of the glomerular membranes change in structure.
Persistent and slowly progressive

Types of MPGN
Type 1 MPGN
Most common Type
Discrete immune deposits in the mesangium and subendothelial space, from circulating immune complexes, this causes mesangial proliferation and extension into the subendothelial zone.
Primary idiopathic MPGN is rare, and diagnosis of exclusion. Should be evaluated for chronic immune complex disease
Thickening of capillary walls,usually global and diffuse.
There is also hypercellularity. Much of this hypercellularity is mesangial proliferation, and some of the capillary wall thickening is caused by mesangial interposition into the subendothelial zone of the capillary loops

Type 2 (Dense Deposit disease)
15-35% of total MPGN cases
Characterized by a pathognomonic electron-dense transformation of GBMs and extensive complement deposition
Immunofluorescence is positive for C3 but negative for immunoglobulins
Recurs after renal transplant over 90% cases
Most have circulating IgG antibody (C3 nephritic factor) that stabilize C3bBb, C3 convertase of alternate pathway, resulted continuous C3 breakdown. – low C3
Higher hypocomplementemia and worse prognosis

Type 3 Mixed features of type I MPGN and membranous GN
Similar to type 1 but subepithelial deposits are prominent and complex disruption of the GBM
Inherited form of type 3 linked to chromosome 1q32

Clinical manifestation
Idiopathic form occurs between ages of 8 and 30
In childhood, type I and II, frequently idiopathic or associated with nephritic factors
In adult, usually type I, commonly associated with cryoglobulinemia and HCV infection
Present with nephrotic range proteinuria or overt nephrotic syndrome, diffuse nephritis with hematuria, edema, hypertension and renal function impairment

Etiology
Primary (idiopathic) vs. Secondary
Autoimmune disorders – SLE, Sjogren’s, Rheumatoid arthiritis, hereditary complement deficient state
Infections – chronic infections rather than acute; Hep B, Hep C, SBE, ventriculoatrial shunt infection, chronic visceral abscess, HIV, schistosomiasis, malaria, leprosy.
Thrombotic microangiopathies – transplant glomerulopathy, antiphospholipid antibody syndrome, TTP/HUS, scleroderma
Others – lipodystrophy, CLL, melanoma, alpha-1-antitrypsin deficiency, non-Hodgkin’s, renal cell carcinoma
Association with HIV in the absence of HCV not well known.

Cardiac Physiology

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Cardiac Reflexes
Baroreceptor Reflex (Carotid Sinus Reflex)
Responsible for the maintenance of blood pressure
Important role during acute blood loss and shock
Volatile anesthetics (particularly halothane) inhibit the heart rate component.
Concomitant use of calcium channel blockers, ACE inhibitors, or PDE inhibitors will lessen the cardiovascular response.
Patients with chronic hypertension often exhibit perioperative circulatory instability as a result of a decrease in their baroreceptor reflex response

Chemoreceptor Reflex
Mediated by
 Chemosensitive cells in the carotid bodies and the aortic body.
 Sinus nerve of Hering and vagus nerve
 Chemosensitive area of the medulla
At PaO2 <50 mm Hg or in acidosis
 respiratory centers stimulated and increasing ventilatory drive.
Activation of the parasympathetic system
 reduction in heart rate and myocardial contractility

Bainbridge reflex
Elicited by
stretch receptors located in the right atrial wall and the cavoatrial junction
vagal afferent signals
Cardiovascular center in the medulla
↑ right-sided filling pressure inhibits parasympathetic activity →↓ heart rate.
Direct effect on the SA node by stretching the atrium.
Depends on the underlying heart rate before stimulation.

Bezold-Jarisch reflex
Elicited by
 chemoreceptors and mechanoreceptors within the LV wall
 Vagal afferents
 ↑ parasympathetic tone
Noxious ventricular stimuli induces the triad of hypotension, bradycardia, and coronary artery dilatation.
Implicated in cardiovascular conditions
 Myocardial ischemia or infarction
 Thrombolysis
 Revascularization
 Syncope
Less pronounced in patients with
 Cardiac hypertrophy
 Atrial fibrillation

Valsalva Maneuver
Valsalva maneuver → ↓CO and BP.
Sensed by baroreceptors → sympathetic stimulation
↑heart rate and myocardial contractility.

When the glottis opens, venous return ↑ →↑BP.
Sensed by baroreceptors → stimulate parasympathetic efferent pathways to the heart.

Hand Palsy

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Ulnar nerve palsy
This occurs due to nerve compression at the elbow (cubital tunnel) or at the wrist (Guyon's canal) (Ulnar canal)
Muscle weakness and atrophy predominate the clinical presentation

Cubital Tunnel Syndrome
Frequent bending of the elbow
Leaning on the elbow, resting it on an elbow,  rest during a long distance drive  or running machinery may cause repetitive pressure and irritation on the nerve.
A direct hit on the cubital tunnel may damage the ulnar nerve

Guyon's Canal Syndrome
A cyst within the canal.
Clotting of the ulnar artery.
Fracture of the hamate bone.
Arthritis of the wrist bones

Symptoms and signs:
numbness and tingling in the ring and little finger and the sides and back of the hand. At Guyon's Canal, sensory supply to the skin of the back of the hand is spared.
The hand may become weaker resulting in trouble opening bottles or jars
Clawing may occur in the ring and little fingers
 Froment's test: by asking the patient to hold a piece of paper between their thumb and index finger (hence checking adductor pollicis). In a patient with Ulnar nerve palsy the interphalangeal joint of the thumb will flex to compensate
Treatment:
Nonsurgical therapy: elbow or wrist splints to limit mobility in addition to an anti-inflammatory drug such as ibuprofen.
Surgical decompression maybe required in some cases

Radial nerve palsy
Causes
Caused by excessive compression of the radial nerve against a hard surface in individuals insensitized by the intake of alcohol or sedatives
Broken humerus
lead poisoning
Stab wounds to the chest at or below the clavicle. Damage the posterior cord of the brachial plexus

Symptoms:
Wrist drop
Occasionally, the back of the hand may lose feeling

Erb’s Palsy
Due to brachial plexus damage, by excessive lateral neck flexion away from sholder:
Forceps delivery
Falling on the neck

Leads to loss of the lateral rotators of the shoulder, arm flexors, and hand extensor muscles.

The position of the limb, under such conditions, is characteristic:
the arm hangs by the side and is rotated medially;
 the forearm is extended and pronated.
The hand is flexed
The arm cannot be raised from the side; all power of flexion of the elbow is lost, as is also supination of the forearm...

Intra Uterine Growth Restriction(IUGR)

Posted by e-Medical PPT

The unborn baby is at or below the 10th weight percentile for his or her age (in weeks). The Foetus is affected by a pathologic restriction in it’s ability to grow.
IUGR almost always leads to Low birth weight (LBW). This is a baby with a birth weight of less than 2.5kg.

SYMMETRICAL IUGR
Less commonly known as global growth restriction.
The baby has grown slowly through out the duration of the pregnancy and was thus affected from a very early stage.
The head circumference of such a new born is proportionate to the rest of the baby.

ASSYMETRICAL IUGR
Embryo /Foetus has grown normally during the first and second trimester but encounters difficulties in the third.
Disparity in the length and head circumference compared to the birth weight.
Head and brain are normal in size but the abdomen is smaller.

Maternal risk Factors for IUGR
Has had a previous pregnancy which resulted in IUGR.
Drugs: Warfarin, Phenytoin and Steroids
Poor weight gain and malnutrition in pregnancy. Tied into social deprivation.
Used substances (Tobacco, Narcotics and Alcohol) resulting in birth defects.
Multiple pregnancy
Antibody problem (SLE ,APAS)
Cardiovascular diseases:
Pre-eclampsia/hypertension.
Cyanotic heart diseases.
Diabetic vascular lesions.
Chronic kidney diseases.
Chronic infections-Malaria, UTI TB, Genital infections...

Indications for Liver Transplantation in Adults:Etiologies of End-Stage Liver Disease

1. Fulminant Hepatic Failure
2. Alcoholic Liver Disease
3. Chronic Hepatitis C
4. Chronic Hepatitis B
5. Non-alcoholic steatohepatitis
6. Autoimmune Hepatitis
7. Primary Biliary Cirrhosis
8. Primary Sclerosing Cholangitis
9. Hepatic tumors
10. Metabolic and genetic disorders

Indications for Liver Transplantation in Adults
Presence of irreversible liver disease and a life expectancy of less than 12 months with no effective medical or surgical alternatives to transplantation
Chronic liver disease that has progressed to the point of significant interference with the patient's ability to work or with his/her quality of life
Progression of liver disease that will predictably result in mortality exceeding that of transplantation (85% one-year patient survival and 70% five-year survival)

Manifestations of End-Stage Liver Disease
Progressive jaundice
Intractable ascites
Spontaneous bacterial peritonitis
Hepatorenal Syndrome
Encephalopathy
Variceal bleeding
Intractable pruritus
Chronic fatigue (such as resulting in loss of gainful employment)
Bleeding diathesis or coagulopathy

Post-operative complications & management of liver transplant patients
Right pleural effusion
 May affect ventilation, necessitating drainage.
Hepatic edema secondary to aggressive resuscitation & increased intravascular volume.
 Goal CVP 6-10. Minimize increased hepatic vein pressures, sinusoidal congestion that impair graft perfusion & exacerbate reperfusion injury.
Renal failure
 Elevation of creatinine & BUN observed in nearly all transplant patients secondary to ATN, hepatorenal syndrome. Usually self-limiting. May necessitate therapy with loop diuretics, renal replacement therapy.
Electrolyte Derangements
 Recovering graft increases demand for magnesium & phosphorous.
Transfusion of citrate rich blood products results in decreased serum magnesium & calcium.
Rapid correction of chronic hyponatremia with isotonic solution can have severe neurological consequence. Judicious use of hypotonic solutions with goal of serum Na 125-130 advised.
Thrombocytopenia
 Preoperative portal hypertension results in splenomegaly & platelet sequestration. Generally improves as graft recovers. May necessitate replacement if bleeding is encountered or invasive procedures are planned. Splenectomy is rarely indicated.
Platelet dysfunction secondary to renal & hepatic failure may be improved acutely with DDAVP.
Biliary leak
 RUQ pain, fever, persistent elevation of bilirubin, liver enzymes. Biloma on CT. Treated with endoscopic stent, percutaneous drainage. Possible surgical revision if duct is ischemic.
Hepatic artery thrombosis
 Persistent elevation or increasing liver enzymes, poor graft function. Diagnosed with U/S, CT angiography, MRA. Treated with immediate revascularization.


Heart Diseases in Pregnancy

Posted by e-Medical PPT

Mortality associated with specific cardiac lesions;
1. Low risk of maternal mortality (less than 1%).
              (a)  Septal defects.
              (b)  New York Heart Association classes I and II.
              (c)  Patent ductus arteriosus.
              (d)  Pulmonary / tricuspid lesions.
2. Moderate risk of maternal mortality (5-15%).
              (a)  NYHA classes III and IV mitral stenosis.
              (b)  Aortic stenosis.
              (c)  Marfan’s syndrome with normal aorta.
              (d)  Uncomplicated coarctation of aorta.
              (e)  Past history of myocardial infarction.

3. High risk of maternal mortality (25-50%).
              (a)  Eissenmenger’s syndrome.
              (b)  Pulmonary hypertension.
              (c)  Marfan’s syndrome with abnormal aortic root.
              (d)  Peripartum  cardiomyopathy.
What is the prognosis for a woman with a cardiac disease depending on the NYHA classification?
Prognosis depending on the functional status
In general, women in NYHA classes I and II lesions
       usually do well during pregnancy and have a
       favorable prognosis with a mortality rate of <1%.
Patients in NYHA classes III and IV may have a
       mortality rate of 5% to 15%. These patients should
       be advised against becoming pregnant.

What are the causes for increased cardiac output during a normal pregnancy?
Cardiac output begins to rise in the first trimester and continues as   steady increase to peak at 32 weeks gestation by 30% to 50% of pre pregnancy level.

Causes for increased cardiac output are
   1. Increases in stroke volume (early pregnancy)
   2. Increase in heart rate (late pregnancy)
   3. Decreased peripheral resistance
   4. Decreased blood viscosity

Physiological changes during labour and puerperium.
          1.First stage.
            Cardiac output increases by15%. Uterine contractions    
            increases venous return , causing increase in cardiac
            output & can cause reflex bradycardia.

         2.Second stage
            Increase in intra abdominal pressure (valsalva’s)
            causes decrease in venous return and  cardiac output.

         3.Third stage
            Normal blood loss during delivery
             (around 250-350  ml).
             It leads to
                a. Decrease blood volume
                b. Decrease cardiac output.
Criteria to diagnose cardiac disease during pregnancy:
    1.Presence of diastolic murmurs.
    2.Systolic murmurs of severe intensity (grade 3).
    3.Unequivocal enlargement of heart (X-ray).
    4.Presence of severe arrythmias, atrial fibrillation or  flutter
The indications for Termination of pregnancy.
 Because of high maternal risks, MTP is indicated in:
1.Eisenmenger’s syndrome.
2.Marfan’s syndrome with aortic involvement
3.Pulmonary hypertension.
4.Coarctation of aorta with valvular involvement.
    Termination should be done before 12 weeks of
       pregnancy.

Preeclampsia: Hypertension >140/90 with proteinuria of at least 0.3g/24h
Severe preeclampsia: Preeclampsia with hypertension >160/110 or proteinuria >5g/24h or multiorgan involvement
Impending eclampsia
Severe preeclampsia with signs of cerebral affection like visual disturbancies, headache, increased reflexes, and clonus
Eclampsia: Convulsions in any woman who has, or then presents with, hypertension in pregnancy of any cause

Symptoms other than hypertension and proteinuria in severe preeclampsia
Oliguria (<400 ml/24h)
Cerebral signs (headache, blurred vision, altered consciousness)
Pulmonary edema, cyanosis
Epigastric or right upper quadrant pain
Impaired liver function
Hepatic rupture
Trombocytopenia
HELLP syndrome

Fetal complications of severe preeclampsia
Intrauterine growth retardation
Premature delivery
Abruptio placentae
Fetal distress

Maternal complications of severe  preeclampsia
Cardiovascular dysfunction (cardiac failure, hypertension)
Renal dysfunction (oliguria, reduced GFR, elevated creatinine, acute tubular necrosis, cortical necrosis)
Respiratory dysfunction (ARDS, pulmonary edema)
Hepatic dysfunction (elevated liver enzymes, subcapsular hematoma, HELLP syndrome)
Cerebral dysfunction (encephalopathy, ischemia, cortical blindness, retinal detachment, infarction, hemorrhage, edema, eclampsia)

”Delivery of the fetus and placenta is the definitive management of severe preeclampsia. Once severe disease has been established and is progressing, delivery of the fetus and placenta must be accomplished to limit maternal risk.”

HELLP syndrome
Microangiopathic hemolytic anemia, consumptive thrombocytopenia, liver dysfunction
4-12% of patients with severe preeclampsia, 30% occur postpartum
DIC often secondary to placental abruption, sepsis or fetal death
Platelet count indirectly proportional to severity of disease
Differential diagnoses: TTP, HUS, SLE, sepsis, acute fatty liver of pregnancy
Complications: ARF, ARDS, hemorrhage, placental abruption, rarely liver hematoma with rupture

Antenatal Monitoring

Posted by e-Medical PPT

Two thirds of fetal deaths occur before the onset of labor.
Many antepartum deaths occur in women at risk for uteroplacental insufficiency.
Ideal test: allows intervention before fetal death or damage from asphyxia.

Uteroplacental insufficiency
 Inadequate delivery of nutritive or respiratory substances to appropriate fetal tissues.
 Inadequate exchange within the placenta due to decreased blood flow, decreased surface area or increased membrane thickness.
 Inadequate maternal delivery of nutrients or oxygen to the placenta or to problems of inadequate fetal uptake.

Conditions placing the fetus at risk for Uteroplacental insufficiency
Preeclampsia, chronic hypertension,
Collagen vascular disease, diabetes mellitus, renal disease,
Fetal or maternal anemia, blood group sensitization,
Hyperthyroidism, thrombophilia, cyanotic heart disease,
Postdate pregnancy,
Fetal growth restriction

Methods for antepartum fetal assessment
 Fetal movement counting
Maternal perception of a decrease in fetal movements / change in the pattern of fetal movements may be a sign of impending fetal compromise.
Cardiff “count to ten” : 10 movements in 12 hours.
Kick charts

 Assessment of uterine growth
Symphysiofundal height
General rule: fundal height in centimeters will equal the weeks of gestation.
Exceptions: maternal obesity, multiple gestation, polyhydramnios, abnormal fetal lie, oligohydramnios, low fetal station, and fetal growth restriction.
Customized chart :Abnormalities of fundal height should lead to further investigation.

 Antepartum fetal heart rate testing
Initial observational studies showed a strong correlation between the abnormal CTG and poor fetal outcome
Widely used as the primary method of
   antenatal fetal assessment
Poor predictive value
High inter-observer inconsistencies

 Biophysical profile
Described by Manning (1980)
The number of biophysical activities that could be recorded increased with real time ultrasound:
Fetal movement (FM)
Fetal tone (FT)
Fetal breathing movements (FB)
Amniotic fluid volume (AFV)
 Doppler velocimetry

IgA nephropathy

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IgA nephropathy (also known as IgA nephritis,Berger's disease) is a form of glomerulonephritis (inflammation  of the glomeruli of the kidney). IgA nephropathy is the most common glomerulonephritis throughout the world.Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus. There are other diseases associated with glomerular IgA deposits, the most common being Henoch-Schönlein purpura (HSP), which is considered by many to be a systemic form of IgA nephropathy. HSP presents with a characteristic purpuric skin rash, arthritis, and abdominal pain and occurs more commonly in young adults (16-35 yrs old). HSP is associated with a more benign prognosis than IgA nephropathy. In IgA nephropathy there is a slow progression to chronic renal failure in 25-30% of cases during a period of 20 years.
The classic presentation  is episodic frank hematuria  which usually starts within a day or two of a non-specific upper respiratory tract infection as opposed to post-streptococcal glomerulonephritis which occurs some time  after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production. Loin pain can also occur. The gross hematuria resolves after a few days, though microscopic hematuria  may persist. These episodes occur on an irregular basis every few months and in most patients eventually subsides (although it can take many years). Renal function usually remains normal, though rarely, acute renal failure may occur.This presentation is more common in younger adults.
Very rarely (5% each), the presenting history is:
    * Nephrotic syndrome
    * Acute renal failure (either as a complication of the frank hematuria, when it usually recovers, or due to rapidly progressive glomerulonephritis which often leads to chronic renal failure)
    * Chronic renal failure (no previous symptoms, presents with anemia, hypertension and other symptoms of renal failure, in people who probably had longstanding undetected microscopic hematuria and/or proteinuria)
A kidney biopsy is necessary to confirm the diagnosis.The biopsy specimen shows proliferation of the mesangium, with IgA deposits on immunofluorescence and electron microscopy.
IgA nephropathy has a very variable course, ranging from a benign recurrent hematuria up to a rapid progression to chronic renal failure. Hence the decision on which patients to treat should be based on the prognostic factors and the risk of progression. Also, IgA nephropathy recurs in transplants despite the use of ciclosporin, azathioprine or mycophenolate mofetil and steroids  in these patients.

Hand Fractures

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Boxer’s Fracture
A break in one or more metacarpal bones, usually the fourth or the fifth, caused by punching a hard object. Such a fracture is often distal, angulated, and impacted
Finger shorten posteriorly

Scaphoid Fracture
Epidemiology
 common in young men; not common in children or in patients beyond middle age
Mechanism
 FOOSH resulting most commonly in a transverse fracture through the waist (middle) of the scaphoid
Clinical Features:
pain on wrist movement
tenderness in scaphoid region (anatomical "snuff box")
usually undisplaced
Investigations:
 x-ray (AP/lat/scaphoid views with wrist exended and ulnar deviation)
+/- bone scan and CT scan
Note: a fracture may not be radiologically evident up to 2 weeks after acute injury, so if a patient complains of wrist pain and has anatomical snuff box tenderness but a negative x-ray, treat them as if they have a scaphoid fracture and repeat x-ray 2 weeks later to rule out a fracture
Treatment:
Undisplaced: cast
Displaced = open (or percutaneous) screw fixation

Colles’ and Smith Fracture
Colles’ Fracture:
Due to FOOSH
> 40 yrs, female (esp. osteoperosis)
Fx fragment: upward-dorsal angulation (fork-like appearance)

Smith Fracture:
Aka: reverse Colles’ fracture
Falling on the back of a flexed hand
Fx fragment: volar (palmar) displacment

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