Subacute Granulomatous Thyroiditis

Subactute Granulomatous Thyroiditis or De Quervain Thyroiditis is an inflammation of Thyroid gland often after an infection of upper respiratory tract that can be characterized by appearance of multinucleate giant cells. Like most Thyroiditis, it affects women more by factor of 4:1.

This type of Thyroiditis is self-limiting and will resolve after a few months. It is associated by infection from measles, mumps, adenovirus, coxsackievirus, etc. It is believed that the virus antigen stimulate CD8+ T lymphocytes activity against thyroid cells damaging the follicles and causing colloid leakage. Because colloid is normally contained inside follicles, the immune system mistake this colloid leakage as foreign material causing macrophage activation. The macrophages then try to engulf and surround the colloid. In the process, they become multinucleate giant cells as seen on above picture.

Graves' Disease

Graves’ disease is an autoimmune disorder in which there is a production of IgG antibodies called thyroid-stimulating immunoglobulin (TSI) directed to TSH receptor which will result in continuous and excessive stimulation of thyroid hormone production and secretion. The symptoms of Graves' disease is typical of thytoxicosis with exopthalmos and pretibial myxedema. Graves' disease affects women more than me up to 10 times. 

 Normal Thyroid

Legends:

1. Follicles with colloid inside 
2. Parafollicular cells or C cells
3. Vein

This is the normal thyroid histology. We can see that thyroid is actually composed of many follicles lined by cuboidal epithelium or low columnar epithelium. When the follicles are actively secreting T3 and T4, the epithelium becomes columnar. The follicles are filled with pink colloid rich in thyroglobulin. We can see that between the follicles, there are some parafollicular cells or C cells. These cells secrete Calcitonin, a hormone that counteract parathyroid hormone (lowering blood Ca²⁺). 

One can see that the epithelium cells lined perfectly with the colloid substance. The black line in the picture represent the attached border of epithelium with the colloid.

Graves' Disease

At first glance, one might not notice any abnormalities in graves' disease. Closer inspection reveals A: cytoplasmic bulging of epithelium cells into the colloid and B: appearance of vacuoles at the edge of the colloids. This "scalloping" causes the border between epithelium cells and colloid not as smooth as in the normal thyroid. All of these findings are caused by increased hormone secretion due to stimulation of TSH receptor. Below is a beautiful picture with more prominent scalloping and cytoplasmic bulging.

How to Differentiate Between Pituitary Hyperplasia and Adenoma

Clinically, hyperplasia can be indistinguishable from adenoma using standard H&E staining. In order to make a diagnosis, one must use reticulin stain. Pituitary cells are surrounded by architecture of reticulin fibers and when the cells undergo hyperplasia, the reticulin architecture s maintained. In adenoma, the reticulin fiber architecture is disrupted. 

 Intact reticulin fiber from pituitary hyperplasia

 Disrupted reticulin fiber from pituitary adenoma

ECG Heart Rate Interpretation

Heart rate interpretation on ECG is one of the most important ability that must be mastered by any medical professionals. Fortunately, it is very easy to calculate this based on ECG.

The horizontal axis of ECG paper represent time and the vertical axis of ECG represent voltage. When we see a blank ECG paper, we will notice there are a lot of squares of varying size. The standard speed of ECG is 25 mm/second. By definition, this means in one second, the ECG will have moved 25 mm. One small boxes equals 0.04 second. This makes 5 small boxes 0.2 second. So in order to complete 1 second, we require 25 small boxes.

There are 3 ways to calculate heart rate based on ECG

For regular rhythm                                              

• using large boxes                                                   
• using small boxes

For irregular rhythm

• Using total QRS in 6 seconds 

Using Medium Boxes

The method for using small boxes:

1. Find R wave that is located exactly or near one of the thick vertical line
2. Calculate the total of large boxes until the next R wave
3. Determine the rate using the formula below 

The formula for using medium boxes :                                      300                                          

                                                               total number of small boxes between 2 R waves

If there is only one large box between two R waves, the duration is 0.2 second (0.04 x 5 small boxes). It means that in one second there is 5 heart cycle and in 1 minute there is 300 heart cycle (5 x 60 seconds).

This is one of the easiest and fastest method but could be the most inaccurate. See those tall R wave that are aligned to the vertical line? Between them are 3 medium boxes.

Using the formula: 300/3 = 100 beats/minute

Using Small Boxes

The formula for using small boxes:                                     1500                                       
                                                           total number of small boxes between 2 R waves

It is very important to utilize this method most of the time since most ECG will not show QRS complexes aligned to thick vertical line. Unless of course you are in emergency room, then feel free to use the first method.

From the example above: 1500/22 = 68 beats/minute

One can also use large boxes method. Between the R wave, there are 4 large boxes + 2 small boxes, making 300/4 = around 75 beats.minutes. A similar result with the first method, is it not? Of course for the math mania can use 300/4.2 from 4 large boxes + 2 small boxes.

On Irregular Rhythm

Count the total of QRS complexes within 6 seconds and multiply it by 10

Irregular rhythm is tricky but still easy. If the QRS complex is irregular just like above from premature atrial contraction, it is not recommended to use small and large box method to determine the heart rate. Instead, we need to take at least 6 seconds of ECG and count the total of the QRS complexes in that 6 seconds. For simplicity, I have marked the ECG above. One must always remember the value of the boxes. 1 small box is 0.04 second, 1 large box equals 5 small boxes. Therefor 1 large box is 0.2 second and 5 large box is 1 second. To make 6 seconds, we need exactly 30 large boxes.

8 QRS x 10 = 80 beats/minute

ECG Of Ventricular Hypertrophy (Will be updated)

Introduction
In this modern age where urbanization and sedentary life has become more common than previously thought possible, there is an increase of numerous health problem such as hypertension, obesity, diabetes, etc while at the same time a decreasing prevalence of infectious disease. Left Ventricle Hypertrophy is an enlargement of myocardium tissue that is strongly related to systemic hypertension. Because of the high prevalence of untreated hypertension, both from undiagnosed patient or poor patient compliance, we can expect an increase of LVH incidence now and in the future. The significance is even greater when we realize that LVH is associated with excess risk of cardiovascular morbidity.

Pathology

Normal, Dilated, and Hypertrophy Heart 

The middle heart is a normal heart. As we can see here, the left ventricle is much more thicker than the right ventricle due to the requirement to pump blood against systemic resistance. Interestingly, infants have their right ventricle thicker due to different hemodynamic physiology during pregnancy (high pulmonary resistance and low systemic resistance). Consequently, this makes the normal ECG interpretation of infants different, a topic that will be discussed in the future. The left ventricle of infant becomes progressively thicker during growth, reaching normal heart structure at teenage years.

The left heart has a hypertrophy of the myocardium, the heart muscle. LVH happens when the required force to pump blood to systemic circulation isn't enough. For example, in systemic hypertension, the muscle of heart requires much greater force to contract than normal in order to counter elevated blood pressure. Another mechanism that can cause LVH is aortic stenosis, an obstruction of blood flow due to narrowing of aortic valve. The obstruction will then make the left ventricle to harder. 

The right heart is a dilated heart, a completely different mechanism yet indistinguishable from hypertrophy in ECG. 

ECG Finding

  

Under normal condition of heart, the left ventricle is electrically more dominant than its right counterpart (negative S waves in right leads and positive R waves in left leads) due to larger mass. So what happens when the left ventricle become really enlarged like from a very long hypertension? Generally, the increase mass of left ventricle will produce an electrical imbalance causing the vector to move even further to left. Because of this, S wave in right precordial leads will have an increase in amplitude (become deeper). Consequently, the leads facing the left ventricle such as I, AVL, V4-V6 are higher than normal.

Repolarization of the left ventricle may also be affected shown by ST segment depression and/or elevation in tall R leads. The T wave is often inverted asymmetrically in left precordial leads. In right ventricle hyperthrophy, the QRS vector is moved to the right

In this illustration, we can see the increased amplitude from Left Ventricle Hypertrophy. Note the high R wave in V6, deep S wave in V1, secondary ST changes in left leads. Also note the high aVL and deep aVR. 

Diagnostic Criteria 

Currently, there are many criteria devised by experts such as from Sokolow to Cornell. This reflect the imperfection of ECG in diagnosing LVH.

Left Ventricle Hyerthropy Criteria
Sokolow-Lyon Voltages	SV1 + RV5 > 3.5mV             RAVL > 1.1mV
Romhilt-Estes point score system See note for score system	Any limb lead R wave or S wave > 2.0 mV (3 points) or SV1 or SV2 ≥ 3.0 mV (3 points) or RV5 to RV6 ≥ 3.0 mV (3 points) ST-T wave abnormality, no digitalis therapy (3 points) ST-T wave abnormality, digitalis therapy (1 point) Left atrial abnormality (3 points) Left axis deviation ≥ −30 degrees (2 points) QRS duration ≥ 90 msec (1 point) Intrinsicoid deflection in V5 or V6 ≥ 50 msec (1 point)
Cornel voltage criteria	SV3 + RaVL ≥ 2.8 mV (for men) SV3 + RaVL >2.0 mV (for women)
Cornell regression equation	Risk of LVH = 1/(1+ e−exp)†
Cornel voltage duration measurement	QRS duration × Cornell voltage > 2,436 mm-sec3 QRS duration × sum of voltages in all leads > 1,742 mm-sec

Note: Probable left ventricular hypertrophy is diagnosed if 4 points are present and definite left ventricular hypertrophy is diagnosed if 5 or more points are present.

Romhilt seems to be the easiest to remember. If you don't like the above criteria, you can use the improvised criteria adapted from above. Below is the summary of them:

1. Amplitude of R wave in V5 OR V6 > 26 mm/2.6mV 
2. Amplitude of R wave in V5 or V6 + S wave in V1 is>35mm/3.5mV
3. Amplitude of highest R wave + S wave in precordial lead is > 45 mm/4.5mV
4. R wave in aVL > 11 mm/1.1mV 
5. R wave in aVF > 20 mm/2 mV
6. S wave in aVR > 14 mm/1.4mV
7. ST wave depression in left precordial
8. Asymmetrical T wave inversion in left precordial 
9. Left axis deviation 

Example 

This ECG fulfills many LVH criteria. Notice in V6, the R wave amplitude exceed 26 mm (more than 5 medium boxes) and of course when we combined the v6 as the highest R wave with V2 as the deepest S wave, the result is more than 45 mm. R wave in AVL more than 11mm.  Not to mention the asymmetrical T wave inversion in V5 and V6. There is a very slight ST segment elevation in V1-V3. This a the kind of ST elevation that may accompany LVH 

Guide to CNS Histology

Cerebellum 40X Magnification – Hematoxylin and Eosin Staining 

Legends:

1.       Medulla of white matter - substansia alba

2.       Granular layer

3.       Purkinje layer

4.       Molecular layer

5.       Meninges – piameter

This is a picture of cerebellum with H&E staining. Cerebellum is divided into medulla and cortex. Medulla is the white matter - substantia alba of cerebellum. Substantia alba consist mostly of myelinated axons and glial cells. Lipids are often washed off during H&E staining. Because of this, some cells and tissue components such as myelin sheath and ground substance are not preserved. The cortex consists of 3 layers – molecular layer, purkinje layer, and molecular layer.

Here we can see the piameter. Piameter is a part of the meninges covering the spinal cord. From the most outer layer is durameter, arachnoidmeter, and piameter.

Cerebellum 100X Magnification – Hematoxylin and Eosin Staining 

Legends:

1.       Cortex of gray matter - substantia grisea

2.       Medulla of white matter - substantia alba

3.       Meninges – piameter

4.       Granular layer

5.       Molecular layer

6.       Purkinje layer

In this picture, we can see the layer much more clearly. Also, the medulla and cortex is highlighted. ________________________________________________________________________________

Cerebellum 400X Magnification- hematoxylin and Eosin Staining 

Legends:

1.       Granular layer

2.       Purkinje cells

3.       Molecular layer

4.       White matter - Substantia alba

This is a high magnification of the cerebellum. The most prominent feature on this slide is the purkinje cells, one of the largest neurons in the human brain. Purkinje cells have dendrite and axons which can be seen depending on the staining used.

Granular layer contains small-size-neuron cell called granule cells with dendrites orienting toward the molecular layer. If the granular layer is looked carefully, there will be some larger cells. These cells are the Golgi cells.

Medulla Spinalis 40X Magnification

Legends:

1. Canalis Centralis
2. Dorsal horn  gray matter 
3. Ventral horn  gray matter 
4. Fissura mediana ventralis  
5. White matter

This is a low magnification of the spinal cord. Spinal cord is part of the nervous system and also consists of gray matter and white matter. Gray matter is located in the central region and divided into ventral and dorsal horn. The outer layer of medulla spinalis is the white matter. In the middle, there is canalis centralis where cerebrospinal fluid flows.

Medulla Spinalis 100X Magnification

Legends:

1.       Canalis centralis

2.       Ependymal cell

3.       Gray matter - Substantia grisea

4.       Sulcus medianus posterior

5.       White matter – Substantia Alba

6.       Fissura mediana ventralis

Here, we can see the Ependymal cells attached to the wall of the central canal. Ependymal cell produces spinal fluid in the central nervous system. They form a single layer of cuboidal to columnar cells that have the morphologic and physiologic characteristics of fluid-transporting cells

Medula Spinalis 400X Magnification

Legends:

1.       Motor neuron

2.     Nucleus

In the ventral horn of medulla spinalis, we can find the motor neuron. Motor neuron transmits action potential to peripheral part of the body. Like other cells, motor neuron also has nucleus.

Legends:

1.       Motor neuron

2.       Axon hillock

3.       Nucleus – prominent nucleolus

4.       Nucleus of neuroglia

5.       Nissl bodies

The axon hillock is characterized by reduced appearance of nissl bodies and surrounding white are that is the myelin sheath lost through staining. Nissl body is actually rough endoplasmic reticulum. In this slide, we can’t see nissl bodies clearly because the cytoplasm looks homogeny. In order to see nissl bodies clearly, a special staining called nissl staining is required.

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 Cerebrum 400X Magnification - Silver Stain

Legends:

1.       Oligodendrocyte

2.       Protoplasmic astrocyte

Oligodendrocyte main functions are to provide support and making myelin sheath in the central nervous system. This function is done by Schwann cell in the peripheral nervous system. Astrocytes are star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries.

There are 2 types of astrocyte – protoplasmic and fibrous astrocyte. In protoplasmic astrocyte, there are a lot of branches of the processes and the cell body can’t be seen clearly because it accumulated the staining substrate. In fibrous astrocyte, there are long thin unbranched processes. Fibrous astrocyte is mainly found at white matter while protoplasmic astrocyte is mainly found at gray matter.

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Cerebrum 400X Magnification - Hematoxylin and Eosin Stain 

Legends:

1. Neurons
2. Astrocytes
3. Oligodendrocytes 

It is important to be able to identify cells in H&E staining. After all, this is the most used staining in the world. Neurons are easy to find but astrocytes and oligodendrocytes can be tricky. The secret is that oligodendrocytes looks like a perfect fried egg. You can see that oligodendrocytes has white halo and dark nucleus similar to fried eggs that have yellow core and white surrounding.