Thyroid Replacement Therapy

Complications of overreplacement with levothyroxine sodium Include the following:

• Accelerated bone loss
• Reduction in bone mineral density
• Osteoporosis
• Increased heart rate
• Increased cardiac wall thickness
• Increased contractility

The last three problems above increase the risk of cardiac arrhythmias (especially atrial fibrillation), particularly in the elderly population.

Medications that suppress TSH production include steroids, dopamine, dobutamine, and octreotide.


Up to 30-40% of patients with hypothyroidism have anemia, usually from decreased erythropoiesis. In 15% of patients, the anemia is of the iron deficiency type, with microcytosis and hypochromia. Although this can be a normocytic normochromic anemia, the most common morphologic abnormality is a macrocytic anemia that may be partially due to insufficient vitamin B-12 and folate intake.


Glomerular filtration rate, renal plasma flow, and renal free water clearance are all decreased in hypothyroidism and may result in hyponatremia.


Prolactin may be elevated in primary hypothyroidism. This is thought to be caused by overlap secretion due to stimulation of the lactotroph by the elevated TRH level. The decreased clearance of prolactin in hypothyroidism may also play a contributory role. The elevated prolactin level leads to decreased gonadotropin secretion and decreased responsiveness to GnRH. The result of this is anovulatory cycles with menstrual abnormalities, galactorrhea, and infertility in some patients.

Other studies may be performed in the evaluation of complications of primary hypothyroidism (when indicated). These tests are usually not performed and are not necessary in routine diagnosis or evaluation of hypothyroid patients.

• Chest radiograph - May show small pleural effusions
• Electrocardiogram (ECG) - May show low-voltage QRS tracing, nonspecific ST-wave changes, and premature ventricular contractions; prolongation of the QT interval with torsade de pointes and ventricular tachycardia may be noted
• Echocardiogram - May show some pericardial effusion in severe cases of hypothyroidism
  
  
  
  

  Long-Term Monitoring

  Upon the initiation of the levothyroxine replacement therapy, check thyroid function tests, specifically TSH, initially every 6-8 weeks as dose adjustments are made. After the attainment of the clinical euthyroid state and a normal TSH level, patients and the TSH levels may be checked every 6-12 months.

  More frequent follow-up and TSH checks may need to be performed when patients start taking medications, such as ferrous sulphate, calcium supplementation, and multivitamins, that have the potential to impair the absorption of levothyroxine and therefore to affect the TSH level. Patients need to be advised to separate these medications from levothyroxine by at least 4 hours.

  Follow-up care should include clinical evaluation for symptoms of hypothyroidism or iatrogenic hyperthyroidism.

  Physical examination should routinely include weight measurement, pulse and blood pressure determinations, and thyroid examination for the presence of nodules.

  Yearly thyroid ultrasonographic evaluation is important in patients with Hashimoto thyroiditis because of the increased risk of thyroid nodules in these patients and for follow-up of patients with existing benign thyroid nodules.

Facies

Hippocratic face (also known as "Hippocratic facies"; eyes are sunken, temples collapsed, nose is pinched with crusts on the lips and the forehead is clammy)
moon face (also known as "Cushingoid facies")
elfin facies - Williams syndrome
Potter facies - oligohydramnios
mask like facies - parkinsonism
Leonine facies - lepromatous leprosy
Mitral facies - mitral stenosis
Amiodarone facies (deep blue discoloration around malar area and nose)
Acromegalic facies - acromegaly
flat facies - down's syndrome
Marfanoid facies - marfan's syndrome
snarling facies - myasthenia gravis
Myotonic facies - myotonic dystrophy
torpid facies - myxoedema
mouse facies - chronic renal failure
plethoric facies - cushing's syndrome and polycythemia vera
'bird-like' facies- pierre robin sequence
ashen grey facies - myocardial infarction
gargoyle facies - hurler's syndrome
monkey facies - marasmus
hatchet facies - myotonia atrophica
gorilla-like face - acromegaly
bovine facies or cow face - craniofacial dysostosis or crouzons syndrome
marshall halls facies - hydrocephalus
frog face - intra nasal disease

Fractures

break in continuity of bone

• Traumatic-sustained due to excessive force-a qualified fracture usually means traumatic fracture
• Pathological-usually trivial-bone already weak by underlying disease
• Displaced fracture may occur due to fracturing force/muscle pull on fracture filaments/gravity-displacement may be shift/angulation/rotation
• Simple/closed
• Compound/open-

1. internal compounding-piercing of sharp fracture end
2. external compounding-lacreation+fracture from outside

• Transverse # fracture line perpendicular to long axis of bone, caused by tapping/bending force
• Oblique #line of # oblique, caused by a bending force which in addition has component along the long axis of the bone
• Comminuted #with miltiple fragments,caused by crushing/compression force along the long axis of the bone
• Segmental # two fractures in same bone@different levels

Fractures with Eponyms

• Monteggia #dislocation #proximal 1/3rd of ulna + dislocation of head of radius
• Galeazzi #dislocation # distal 1/3rd of radius with dislocation of distal radio-ulnar joint
• Night stick # isolated # shaft of ulna
• Colles' # occuring in adults@cortico-cancellous junction of distal end of radius + dorsal tilt & other displacements
• Smith's # occur in adults@cortico-cancellous junction of distal end of radius with ventral tilt & other displacements (reverse Colles')
• Barton's (marginal) # intra-articular# through distal articular surface of radius, taking a margin, anterior/posterior of the distal radius with the carpals displaced anteriorly/posteriorly
• Chauffeur's # intra-articular oblique # of styloid process of radius
• Bennet's # dislocation-oblique,intra-articular # of base of 1st metacarpal with sublaxation of trapezio-metacarpal joint
• Rolando # extra articular # of base of 1st metacarpal
• Boxer's # a ventrally displaced # through the neck of the 5th metacarpal-common in boxers
• Side swipe # an elbow injury, combination of #distal end of humerus with # proximal end of radius &/or ulna (baby car #)
• Bumper # comminuted depressed type-lateral condyle of tibia
• Pott's # bimalleolar ankle
• Cotton's # trimalleolar ankle
• Massonaise's # ankle with # neck of fibula
• Pilon # comminuted, depressed intra-articular # distal end of tibia
• Aviator's # neck of talus
• Chopart # dislocation # dislocation through inter tarsal joints
• Jone's # Avulsion # base of 5th metatarsal
• Jeffersen's # 1st cervical vertebra
• Whiplash Injury- cervical spine injury involving sudden flexion followed by hyperextension
• Chance # also called seat belt #, line of # runs horizontally through the body of vertebra through & through to the posterior elements
• March # fatigue # of shaft of 2nd & 3rd metatarsal
• Burst # comminuted # of vertebral body where fragments burst out in different directions
• Clay-Shoveller's # an avulsion # of spinous process of one or more of the lower cervical or upper thoracic vertebra
• Hangman's # pedicle & lalamina of C2 vertebra, with sublaxation of C2 over C3-sustained in hanging
• Dashboard # posterior lip # of acetabulum, often associated with posterior dislocation of hip
• Straddle # bilateral superior & inferior pubic rami #
• Malgaigne's # a type of pelvis # in which there is a combination of #s- pubic rami anteriorly & SI joint/ilium posteriorly, on the same side
• Mallet Finger- a finger flexed at the DIP joint d/t avulsion or rupture of extensor tendon@base of distal phallanx

Skin: Histology

Continually renewing stratified squamous epithelium-keratinizes & gives rise to derivative structures called appendages (pilosebaceous units, nails & sweat glands)

Cell Cycle-G0-G1-S-G2-M

Keratinocyte-ectodermally derived cell constituting 80% of epidermal cells-keratin filaments are hallmarks of keratinocytes & other epithelial cells

Immigrant cells- Melanocytes& Langerhans cells(migrate into epidermis during embryonic development), Merkel cells(differentiate in situ)

Melanocytes- located in stratum basale(stratum germinativum)- project their dendrites into epidermis- transfer their melanosomes (melanin packed membrane bound organelles) to keratinocytes which contains majority of melanin pigment - 36 keratinocytes per melanocytes- epidermal melanin unit

Keratinization- genetically programmed, carefully regulated, complex series of morphological changes & metabolic events that occur progressively in postmitotic keratinocytes & involve-

• increased cell size & flattening
• appearance of new cellular organelles & structural reorganization of those present
• change from generalized cellular metabolism to a more focussed metabolism associated with the synthesis of molecules related to keratinization(structural proteins & lipids)
• alterations in properties of plasma membrane, cell surface antigen & receptors
• eventual degradation of cellular organelles including internucleosomal chromatin fragmentation characteristic of apoptosis
• dehydration

Epidermal Layers

• Basal layer/stratum germinativum-attached to basement membrane-contains mitotically active keratinocytes-contains house keeping organelles(RER,golgi complex, mitochondria, lysosomes & ribosomes)-gives rise to superficial layer
• Spinous layer/Stratum spinosum-named for spine like appearance of cell margins in histological sections. Spines are abundant desmosomes, calcium dependent cell surface modifications that promote adhesion of epidermal cells & resistance to mechanical stress.Upper spinous layer cells have organelles called lamellar granules
• Malpighian layer-includes both basal & spinous layer
• Granular layer/stratum granulosum-characterised by buildup of components necessary for the process of programmed cell death & formation of a superficial water impermeable layer.The most apparent structures within these cells are-basophilic keratinohyaline granules-composed of profilaggrin,keratin intermediate filament & loricrin. Conversion of profilaggrin to filaggrin(filament aggregating protein)-occurs during transition of granular to cornified cells
• Corny layers or Stratum corneum- formed of cornified or horny cells which is the largest of epidermis & have highest concentration of free amino acids,esp in mid layers.Stratum corneum cells retain some metabolic function (not just an inert covering)

Normal turnover time of epidermis/skin doubling time-- 4wks

VLBW/premature infants lack-stratum corneum

Carpal Tunnel

• Carpal tunnel or carpal canal is the passageway on the palmar side of the wrist that connects the forearm to the middle compartment of the deep plane of the palm

• The canal is narrow and when any of the nine long flexor tendons passing through it swells or degenerates, the narrowing of the canal often results in the median nerve becoming entrapped or compressed, a medical condition known as carpal tunnel syndrome

• The structures passing through it are

1. flexor digitorum profundus (four tendons)
2. flexor digitorum superficialis (four tendons)
3. flexor pollicis longus (one tendon)

A single nerve passes through the tunnel: the median nerve between tendons of flexor digitorum profundus and flexor digitorum superficialis

The carpus, the bony elements of the wrist, form an arch which is convex on the dorsal side of the hand and concave on the palmar side. The groove on the palmar side, the sulcus carpi, is covered by the flexor retinaculum, a sheath of tough connective tissue, thus forming the carpal tunnel. The flexor retinaculum is attached radially to the scaphoid tubercle and the ridge of trapezium, and on the ulna side to the pisiform and hook of hammate

The narrowest section of the tunnel is located a centimetre beyond the mid-line of the distal row of carpal bones where the sectional area is limited to 1.6 cm²

The tendons of the flexor digitorum superficialis and profundus pass through a common ulnarsheath, while the tendon of the flexor pollicis longus passes through a separate radial sheath. Themesotendon shared by these tendons is attached to the radial and palmar walls of the carpal tunnel

Superficial to the carpal tunnel and the flexor retinaculum, the ulnar artery and ulnar nerve pass through the ulnar tunnel

Movements in the wrist affects the shape and width of the carpal tunnel. The width decreases considerably during normal range of motion in the wrist and because the carpal bones move in relation to each other with every motion of the hand the bony walls of the tunnel are not rigid. Both flexion and extension increase compression in the carpal tunnel:

• Flexing the wrist causes the flexor retinaculum to move closer to the radius which considerably decreases the cross section of the proximal opening of the tunnel. Additionally, the distal end of the capitate presses into the opening.
• In extreme extension. the lunate constricts the passage as it is pressed toward the interior of the tunnel.

Biosimilar Insulins

Biocon is conducting Phase-3 trials of recombinant human insulin (biosimilar of Novo Nordisk’s Novolog) in Europe and global Phase-1 trials for glargine (biosimilar of Sanofi-Aventis’ Lantus). Biocon will continue to develop other biosimilars — aspart (biosimilar of Novo Nordisk’s Novolog) and lispro (biosimilar of Eli Lilly’s Humulog)

Eye: Anatomy

Outer Layer- cornea/sclera

anterior part of sclera covered by mcous menbrane-the conjunctiva

Cornea:

• 3 layers-epithelium, substantia propria(stroma),Descemet's membrane with endothelium
• epithelium-stratified, basal cells lie on Bowman's membrane
• stroma-90% of corneal thickness - regularly arranged thin fibrils of collagen ensheathed by acid mucopolysaccharides set in a ground substance- form ribbon like bundles & give the stroma a laminated appearance- fibrils circular in CS-spaced equidistant- hexagonal lattice
• transparency related to regularity of stromal components-interfibrilar spacing less than a wavelength of light-tangential rows of fibres act as diffraction gratting resulting in destructive interference of scattered rays
• Descemet's membrane-thin elastic membrane-covered on posterior surface by endothelium
• stromal hydration maintained by endothelium- electrolytes removed & water flows passively
• endothelium examined by 500x specular microscope
• endothelial cells decrease in number with age-residual individual cells enlarge to compensate
• corneoscleral junction- limbus- cornea set into a sclera like a watch glass
• nerve supply-trigeminal
• no blood vessels- minute arcades @ limbus (1mm)
• corneal nourishment- diffusion of aqueous humour & peripheral vessels

Lining the Inner Aspect of Sclera-

1. Uveal Tract-highly vascular-for nutrition
2. Retina

Uveal Tract:

• Choroid
• Ciliary Body
• Iris- anteriormost

Anterior Chamber:

• aquous humour
• between cornea & iris 2.5 mm deep in centre
• peripheral recess- angle of anterior chamber
• canal of Schlemm- circular venous sinus in inner layer of sclera- often more than one lumen
• trabecular meshwork between canal of Schlemm & recess of anterior chamber

Iris:

• anterior surface-single layer endothelium-not continuous@crypts
• stroma contains branched connective tissue cells
• iris stroma usually pigmented-unpigmented in blue sclera
• blood vessels in iris-radial
• tissue spaces communicate directly with anterior chamber through crypts@ ciliary border
• thinnest@attachment to ciliary body
• posterior surface-2 pigmented epithelium-developmentally from retina-continuous@pupillary margin-anterior layer flattened cells-posterior layer cuboidal cells
• pupillary smooth muscles derived from from anterior epithelial cells
• sensory- trigeminal
• sphincter pupillae-occulomotor
• dilator pupillae-sympathetic (cervical chain)

Ciliary Body:

• like isosceles triangle- base forwards
• chief mass-ciliary muscle-unstriped-3 parts-circumferential-blends with scleral spur
• most muscles meridional in anteroposterior direction, 2nd portion v-shaped interdigitating concentrically@base of iris, 3rd portion -insertion@ root of iris-just anterior to pigmentary epithelium-closely related to dilator muscle
• anterior surface-corrugated-pars plicata-contains ciliary processes(tufts of blood vessels-like glomeruli) in between
• posterior part-smooth-pars plana
• covered on inner surface by 2 layers of epithelium-belongs to retina-only outer layer pigmented
• posterior extent-ora serrata-transition from ciliary body to choroid gradual
• ora serrata more anterior on nasal side than temporal
• sensory-trigeminal
• motor-occulomotor & sympathetic

Choroid:

• extremely vascular membrane in contact everywhere with sclera with a potential space-epichoroidal/suprachoroidal space in between
• inner side lamina vitrea/membrane of Bruch
• blood vessels increase in calibre from inside to outside-choriocapillaries(fenestrated vessels) immediately beneath membrane of Bruch
• sensory-trigeminal
• autonomic supply-for vasomotor

Retina:

• Outer layer epithelium-hexagonal single layer pigment epithelium
• Inner layer epithelium-suddenly changes@ora serrata into highly complex visual retina

Retina formed by 3 strata of cells & their synapses:

• visual cells-externally
• relay layer of bipolar cells-intermediate
• ganglion cells-internally

1. pigment epithelium-hexagonal cells-single layer-assist metabolism of retina- products of metabolism are freely exchanged between receptor cells & pigment epithelium-melanin granules prominent(absorbs light)-phagosomes present-
2. rods & cones-neural epithelium-discs renewed continuously-rod discs have limited life,eventually lost to pigment epithelium
3. external limiting membrane-perforated by rods & cones
4. outer nuclear layer-nuclei of rods & cones
5. outer plexiform layer-synaptic layer-transmissive region
6. inner nuclear layer-nuclei of bipolar cells-
7. inner plexiform layer-synaptic
8. ganglion cell layer
9. nerve fibre layer-axons of ganglion cells running centrally to optic nerve
10. internal limiting membrane-separates retina from vitreous

• Fibres of Muller-better developed vertical cells-supportive neuroglial cell- nutritive function

• Fovea Centralis- at posterior pole (3mm in the temporal side of the optic disc)-only cones present- other layers almost completely absent- most sensitive part of retina

• Macula lutea(yellow spot)-surrounds fovea centralis-nuclear layers get thinned out-plexiform layer present-ganglion cells heaped up into several layer(in stead of consisting of a single row of cells)-no blood vessels present-nourishment entirely by choroid)-more sensitive than other parts of retina,less than fovea

• Optic Disc-fibres of nerve fibre layer pass into the optic nerve-other layers of retina stop abruptly@ the edge of the aperture in the scleral canal- spanned by transverse layer of connective tissue containing much elastic tissue(lamina cribrosa)-through its meshes the optic nerve fibres pass-on posterior side the nerve fibres abruptly become surrounded by medullary sheaths

Lens:

Biconcave mass of peculiarly differentiated epithelium-developed from invagination of surface ectoderm of the fetus(compare with plantar corns)-original surface goes inside@centre-peripheral cells correspond to the basal cells of epidermis-inner old cells undergo sclerosis-changes analogous to that of stratum granulosum in epidermis-becomes massed together in the form of nucleus-Lens is devoid of nerve supply

1. Accommodation is one of the focusing mechanisms of the eye.
   Accommodation
2. In order to focus rays from objects at varying distances, the lens must change it's refractive power.
3. To change it's refractive power, the lens changes shape
4. The exact shape of the lens is determined by seventy or so suspensory ligaments.
5. The suspensory ligaments attached to the lens are called zonula.
6. The zonula are attached radially around the lens.
7. The zonula pull the edges of the lens towards the clilary body.
8. When the eye is accommodated for distant vision, both the circular and meridional fibres of the ciliary muscle are relaxed. (a)
9. When both the circular and meridional fibres of the ciliary muscle are relaxed, the zonula is stretched.
10. When the zonula is stretched it pulls the elastic lens into a flattened shape.
11. When the eye is accommodated for near vision, both the circular and meridional fibres of the ciliary muscle contract. (b)
12. When both the circular and meridional fibres of the ciliary muscle contract, the tension in the zonula is released.
13. When the ciliary muscle contracts, the ciliary process and choroid move forward toward the lens.
14. When the tension in the zonula is released, it allows the the elastic lens to bulge.
15. The lens of the eye is elastic.
16. Because the lens is elastic, it bulges, shortens, and thickens.
17. The ciliary process is the aqueous humor factory.
18. The aqueous humour is drained out of the scleral venous sinus.