What are the different kinds of seizures

About 2.5 million people in North America have active epilepsy, leaving them susceptible to seizures. However, not all epileptic seizures are the same. They can range in intensity from non-serious to seriously life-threatening.

During a seizure, a person may lose a certain degree of consciousness, called impaired consciousness, and may also experience an episode of intense, widespread motor activity called a convulsion. A convulsion can occur without loss of consciousness, but not normally.

A seizure happens when the way the brain functions is somehow abnormal causing the impaired consciousness or convulsions. When they happen at the same time, you'd call them a convulsive or sensory seizure.

Epilepsy is diagnosed when brain disfunction is disturbed for a relative while or if someone is particularly prone to seizures. You have to have at least two seizures that are not caused by something else, like a disease, before the diagnosis is made.

Now, as for the different types:

- A partial seizure is one that is localized in a specific set of brain structures, where as a generalzied seizure involves widespread abnormal brain activity such as happening in the cerebral cortex of both brain hemispheres.
- A tonic-clonic seizures are the most common, and often called grand mal seizures. They are generalized convulsive seizures where one also loses consciousness. They occur in phases: The tonic phase is when there's a stiffening of muscles, then the clonic phase is when there's relaxation -- the result are muscle spasms of contraction/relaxation of muscles.
- A myoclonic seizure is when you have muscle twitching or limb jerking. It's generally due to problems with cortical activity in the brain. It's localized. But sometimes, myoclonic jerks can involve upper limbs or the entire body being thrown about.

Some nonepileptic seizures occur. They include those tonic-clonic seizures that happen after withdrawal from sedatives or hypnotic drugs. If the seizures come in a chain of patterns, then it's called status epilepticus. Other nonepileptic seizures can happen because of bacterial meningitis, renal or hepatic failure, hypoxic encephalopathy, fever, brain tumors or cerebrovascular accidents. Nonepileptic seizures are usually not a concern once underlying cause is treated.

On the other hand, epileptic seizures are primary from epilepsy. Their origins are in the gray matter of the brain, or, actually, the cortical tissue that forms the hippocampus, which is necessary for memory. The neurons in the cortex that give rise to excitatory outflow are the pyramidal cells, which are kind of pyramid shaped.

The pattern of a seizure is usually pretty predictable. It starts with a prodrome, or warning symptoms like a mental, motor or sensory phenomena called an aura, which a person might remember happened last time a seizure occurred. Then, the seizure happens and depends on type, as explained above.

A partial seizure will either have a focal motor without march, in which the seizure comes from neurons in the motor cortex that leads to twitching on the hand or a side of the face and doesn't spread across. Or, it may have a focal motor with march, which happens when the twitching spreads to the upper arm, shoulder and face. If the spread is limited, then it's called a simple partial seizure.

Complex partial seizures can result of a change in consciousness after a simple partial seizure, with resulting "automatisms," like lip smacking, sucking, chewing, fumbling, incoherent talking, etc, which have no apparent purpose. When these occur, it's highly possible they arise from the temporal lobe.

If the partial seizure progresses, it may end up becoming a generalized tonic-clonic seizure with a full episode including loss of consciousness.

A generalized seizure doesn't have any specific focus, so generally includes seizures that vary a lot. Absence seizures are a type of generalized seizure in that they involve an appearance of absence, like a blank stare for about two to ten seconds along with lip smacking, chewing, etc. A simple absence is common in childhood or adolescence epilepsy. An absence variant is associated with Lennox-Gastaut, which usually results from mental retardation in children.

The tonic-clonic, or grand mal seizures, are a maximal seizure response in the brain. It is generalized because it involves both hemispheres and is usually has a prodrome. The prodrome could be depression, irritability, sometimes euphoria (as Dostoyevsky expressed saying that seizures began with ecstasy). The seizure, again, has a tonic phase of about 10-20 seconds with muscle flexing, with sometimes an epileptic cry. Tthen a 1/2 to 2-minute clonic phase of relaxation. Then these phases are followed by a terminal phase for 5 minutes when the patient goes into something like a coma, going totally limp and quite.


Diagnosis involves an electroencephalograph, or EEG, as well as CT scans or magnetic resonance imaging (MRI) (which are more effective than CT scans). The EEG will determine characteristic interictal (period of time between seizures) abnormalities. A MRI could identify structural abnormalities in the cortex.

Medical treatment and seizure-coping strategies may involve pharmaceutical agents as well as simple stress-reduction techniques, plus routine EEGs and seizure monitoring with CT or MRI.

Reference

Nowak et al.

What are the differences between types of headaches

If there's one thing that will give you a headache, it's trying to remember all of the different kinds of headaches are, and what are their causes or what are they associated with, which can involve simply drinking too much, smoking, stress or fatigue to food poisoning, fever, carbon monoxide poisoning, hypothyroidism, and so on.

Basically, any headache is generated pain originating from structures in the head such as the venous sinuses, the tributary veins, the dura at the base of the brain, the arteries within the meninges, or the subarachnoid space. These are all sensitive to stimulation and cause pain. Plus, there are trigeminal, vagus, and upper cervical nerves that can cause pain if under tension, inflamed or compressed.

Tension headaches are the most common. They're also very poorly understood and not treated very effectively. They happen just from fatigue, stress, worry. Usually they go away with stress-reduction techniques and relaxation, antidepressants or antianxiety drugs. They can last for a night, for a week, or even for years. It usually feels kind of like you have a gradual increase in nonthrobbing pressure or tightness in the head, which varies in intensity.

Migraines are a different story. For one thing, it's localized to one side of your head, like behind an eye or ear, and can result in throbbing-to dull pain and nausea or vomiting. Usually, children and young adults get them, as well as women beginning a premenstrual part of their cycles. A migraine is thought to happen due to arteriolar constriction and decreased blood flow in the head.

A classic migraine will have some typical foreboding with cravings, drowsiness or depression, and include light sensitivity or bright zigzag lines. The migraine usually lasts about 20 to 30 minutes.

A complicated migraine, or neurological migraine, involves symptoms similar to classic migraine, but with neurological symptoms. The extras include lip, face, hand and leg tingling as well as weakness or paralysis (like a stroke). There may be problems with a person's speech. It can last minutes or hours.

Cluster headaches can be difficult to treat. They are like migraines, but happen usually two or three hours after falling asleep. The person wakes up with steady, intense pain in an orbit and with flowing tears and one stuffed nostril that runs later on in the day. He or she will also probably have a constricted eye pupil, a drooped eyelid and a flushed cheek on the same side. The whole episode can last 10 minutes to 2 hours. Treatment can include antidepressants or corticosteroids. It's often called the "suicide headache" because of its intensity.

Reference

Nowak et al.

What’s the difference between systemic, essential and secondary hypertension?

Our arteries are origins of potential disease and death. Most of arterial disease happens through sclerosis, or a hardening of the arteries. Previously we called this arteriocleoris, but that’s too general. So now, sclerosis is defined as either medial calcific sclerosis, hypertensive vascular disease or atherosclerosis.

Hypertensive vascular disease, in particular, is also called arteriosclerosis because it involves arteriole’s intima and media thickening as a result of cumulative amounts of plasma proteins,plus overproduction of basement membrane and extracellular matrix.

Systemic hypertension, or high blood pressure, is associated with hypertensive vascular disease and is a problem that is widespread. The term systemic distinguishes the condition from a local high blood pressure as in pulmonary (lung) or portal hypertension (hepatic portal system). The chief risk factors are genetics, race, older age, smoking, obesity and stress.

Essential hypertension does not usually have an identifiable cause, but is just a defect in mechanisms that control blood pressure. It may involve a defect in the kidney’s ability to excrete sodium, a defect in the arteriolar smooth muscle, or a defect causing exaggerated response of autonomic system.

Secondary hypertension results as a secondary aspect from a disorder such as kidney damage that causes elevated blood pressure.

The consequences of hypertension are both arteriolosclerosis (reduced arteriole’s lumen) and possible stroke or heart attack.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

Thrombosis and thromboembolism

When there’s a problem in normal blood flow, we call it a hemodynamic disorder. They are caused when there’s an overcoagulation of blood forming a thrombus in side a vessel. The process is called thrombosis, which can also result in embolism or infarction.

When a thrombus forms, it’s made up of platelets, erythrocytes, leukocytes and fibrin. It doesn’t form outside a blood vessel as clots do, but instead forms at a blood vessel wall. The thrombosis begins at a point attached to the vascular wall where platelets group together.

A coagulation cascade is triggered, but there’s no threatened blood loss. How does this happen? Endothelial damage, altered blood flow, or a state of blood hyper coagulation.

Endothelial damage can result from hemodynamic stress as blood flow under pressure causes arteries to expand and elongate. The pressure can be produced due to hypertension, a major cause.

But a second major cause is atherosclerosis.

Abnormal blood flow can cause more platelet contact with endothelium, which reduces rate of flow or stops it completely. The change can produce risk of adherence causing thrombosis.

Blood hypercoagulation is a situation when blood is highly susceptible to coagulation despite whether or not there is endothelial damage. It can occur when malfunction in systems, which may be due to immune system problems or liver overproduction of clotting factors.

Older people may have a deficiency of a coagulation inhibitor. Smokers and obese people may have hypercoagulation problems, but the mechanisms are not well understood.

Thrombosis ultimately results in a sequela of either resolution, organization, propogation, infarction or embolism.

Resolution is when the anticoagulation system is seeking to overcome the problem and is least threatening.

Organization happens when phagocytic digestion of a thrombus occurs about two or three days after the thrombus forms. An endothelium forms over the organizing tissue and the thrombus simply becomes part of the vascular wall. While this happens small channels sometimes are created for blood to pass through the thrombus through a process called recanalization.

Propagation is when a thrombus enlarges going along a vessel (a vein usually) and a red cap is produced along the vein’s lumen.

Infarction is when ischemia (when lumen is completely blocked by the thrombus) produces necrosis of a region. This is the most serious in arteries since they supply oxygen and nutrients.

Embolism is when a blood vessel is occluded by an embolus, when a mass of some sort is going along in the blood stream, which is usually result of a thrombus breaking away (as in thromboembolus).

Anticoagulatns, like heparin, are commonly used as therapy to avoid thromboembolism .

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

Blood: Circulating Life

Blood is a fluid that is made up of plasma and elements, which includes erythrocytes, leukocytes and platelets. At times the plasma volume and concentration can be affected as in fluid and electrolyte imbalances, but other times blood coagulation can have its disorders.


When elements are produced in the blood, we call this hemopoiesis. Hemopoiesis takes place through mitosis and differentiation of daughter cells. The cells specialize to produce a specific function. Most of the hemopoiesis happens in red bone marrow (about 2 liters of red marrow is in an adult’s skeleton). Formed element has very little reproductive abilities.

Stem cells are able to differentiate into all hemopoietic cells, or even form new stem cells. Progenitor cells are derived from stem cells but can’t self-renew themselves, so are said to be commited to a cell line.

Erythropoises, red blood cell formation, happens through mitosis. Then hemoglobin synthesis happens, followed by loss of organelles. The reticulocyte is finally a mature erythrocyte once cytoplasmic RNA is lost. It lasts about 120 days before removal in spleen, liver or marrow. Twenty five billion are lost every day, so production is about just as high.

Leukopoiesis happens in granulocytes and moncytes, with migration of lymphocyte progenitors to lymphoid tissue. We have about 7 million of these white blood cells in each milliliter of blood.

Thrombopoiesis produces thrombocytes, or platelets, from marro megakaryocytes. It happens through fragmentation as cytoplasm fragments are shedded from the megakaryocyte. There’s about 250 million platelets per milliliter.

Coagulation

Coagulation of blood is a response that occurs to block blood loss and basically is a turning of fluid blood to a gel so it stops flowing. The gel is a blood clot. It’s created with long protein filaments that become a tangled mesh next to wherever damage happened. The filaments are made of fibrin, derived from fibrinogen, which is split by thrombin, an enzyme derived from prothrombin. The thrombin also activates factor XIII to create crosslinking of fibrin filaments.

Prothrombin is activated to produce thrombin by a cascade of events that are a result of clotting factors. The clotting factors hang out in the plasma, but are only activated when endothelial cells or fibroblasts at a damaged sites have membrane changes that spills out tissue factor, or tissue thromboplastin.

Tissue factor activates the extrinsic pathway, clotting factors activate, and fibrin starts coagulation. The thrombin also stimulates another cascade called intrinsic pathway, which triggers even larger amounts of fibrin production.

Calcium is required for coagulation but only a little bit so a calcium deficiency is unlikely to affect response. The calcium is taken up by chelating agents . The liver contributes fibrinogen, prothrombin and clotting factors in a way that requires vitamin K.

Bleeding Disorders

A bleeding disorder can occur when there are issues with platelet or clotting factors. Thrombocytopenia is a condition that occurs when there aren’t enough platelets.

Clotting factor disorders can include Von Willebrand’s disease when a factor interferes with platelet binding or hemophilia when there are deficiencies in clotting factors.

Impaired hepatic synthes occurs when liver cannot produce enough clotting factors such as due to deficiency of vitamin K or if liver damage causes abnormal clotting factors to be produced.

Sometimes bleeding disorders can occur from small blood vessels as in vascular purpura, which is a blood vessel abnormality.

Erythrocyte disorders

When there are too many erythrocytes, we have polycythemia; and when there are too few, we have anemia.

Anemia can happen due to little oxygen transport, iron deficiency, B12 deficiency, folic acid deficiency, or due to hemolysis because of abnormal blood cells (sickle cell, thalassemia).

Polycythemia can involve overproduction of red blood cells in the marrow. Smokers can suffer secondary polycythemia when inhaling carbon monoxide because it binds to hemoglobin causing compromised oxygen delivery, which can trigger increased erythrocyte production.

Leukocyte disorders

Like in erythrocytes, there may be too many leukocytes (leukocytosis) or too few (leukopenia).

Leukopenia usually happens because of neutropenia, when white cells are depleted because of infection or not enough production from marrow because of anti-tumor drugs or radiation.

Leukocytosis happens when there’s increased demand to a inflammation.

Leukemia is a cancer that results when a leukocyte precursor turns into a malignant tumor, then spill to the blood.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

Growth of Tumors

When an overgrowth of tissue forms into neoplastic mass, it’s called a neoplasm or tumor. Neoplasia can have a deadly outcome such as in cancer. It is the No. 2 killer in North America with 30 percent suffering from the disease. A quarter of North American adults die of cancer. It also kills more children than any other disease.

Oncology is the study of tumors and when we talk about tumors, there’s two important characteristics – pattern of growth and tissue of origin. A tumor is benign if growth is slow, orderly and the tumor is localized. It’s malignant if the growth is rapid, disorderly and invades other normal tissues. Cancer is result of a malignant tumor that spreads to distant points in the body.

We add the suffix “-oma” when designating a benign tumor and what in which tissue it originates. An osteoma is a benign tumor in bone. A fibroma is a benign tumor in fibrous tissue.

If a malignant tumor arises, then it is named depending on which embryonic tissue it originates from. If from the ectoderm or dndoderm, then it’s a carcinoma (usually skin and epithelial linings). If it’s a glandular tumor, then it’s called an adenocarcinoma. If it occurs in the mesoderm, then it’s a sarcoma such as a chondrosarcoma or fibrosarcoma.

Then, there are exceptions, such as melanoma, lymphoma, and hepatoma which sound benign but are actually malignant. Malignant tumors in leukocyte-producing tissues are myeloid leukemia (red bone marrow) and lymphcytic leukemia (lymphoid tissue).

A benign tumor’s cells are about normal size and shape and pretty much looks like normal tissue, but a malignant tumor is very pleomorphic, enlarged and contains abnormal nuclei and chromosome structures. Sometimes the cells are huge because they fail to undergo mitosis.

Benign tumors grow faster than normal, but are slower than malignant tumors. They also have a fibrous connective tissue capsule surrounding the mass, which creates a distinct line to separate it from normal tissue. Generally, the slow growth causes less damage and surgical removal leads to a pretty good prognosis.

Malignant tumors grow quickly and are aggressive in their invasion. They send whole columns of cells to disrupt other normal tissues. They rarely come within a capsule as the benign tumors do. The line is blurred between malignant tumor tissue and normal tissue. Metastasis is a major factor causing a poor prognosis as growth at primary sites usually lead to establishment of tumors in secondary sites.

A spread of malignant tumor to secondary sites increases damaging effects. The metastasis of tumor cells often are carried by blood or lymph. If the invasion of a vein or lymphatic vessel occurs, then an emboli is formed that is used to gain access to a secondary site. Capillaries and lymphatic vessels are easily invaded, especially by carcinomas.

Metastasis can also involve spreading through body cavities. These can include adenocarcinomas shedding from the pancreas into the pelvic cavity or when a neuroblastoma from a the medulla oblongata spreads to the subarachnoid space invading the spinal canal.

Iatrogenic metastasis is rare. It occurs when medical intervention introduces tumor tissue to a site to develop into a secondary tumor.

Tumors growth at primary and secondary sites impairs normal functions. Malignant tumors cause continual increased damage, which generally overwhelm the body despite therapy.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

How the healing process really happens

Healing is a pretty fascinating process that our body is capable of producing all on its own in response to destroyed tissue. The process replaces lost tissue and restores structure, strength and function. It’s intertwined with inflammation and so there’s overlap between the responses as you’ll note after reading these posts and previous ones.
It all happens when tissue that is undamaged next to the damaged tissue begins to proliferate. Functional cells called parenchyma combine to form a stroma. Then, there’s two different ways healing takes place: regeneration or repair. Regeneration is when tissue is replaced. Repair is when fibrous car tissue is used to fill gaps.

Basically, reestablishing epithelium at damaged spots come with four components:

- Regeneration: This is when cells lost are replaced by mitosis by adjacent parenchymal cells. It’s ideal because new tissue is ideal for normal function.

- Repair: This is when fibrous connective tissue, or a scar (made of strong collagen) is used to restore structure, but can’t regenerate. Fibroblasts are up to the task of creating fibrosis since they tend to resist damage from injury.

- Revascularization: Despite whether or not regeneration or repair has happened at the site of injury, revascularization, or angiogenesis, restores blood supply. It is the process of production of new blood vessels coming to the site to supply nutrients.

- Surface restoration: When mitosis is happening at a site of injury, the new cells migrate to the edge and onto the surface where the injury is. They begin to organize secreting new basement membrane and when the edges meet, they become anchored in the membrane.

Primary healing is what we say to describe healing of a severing of a wound, or incision. There’s only minor damage with wound edges close to eachother. Bleeding narrows the gap, a clot forms, then a scab, an exudates and then a newly restored surface.

Secondary healing happens when wounds’ edges are not so close. They can happen commonly in skin and the GI tract (such as from a duodenal ulcer). The large wounds produce a lot more debris. The restoration process is extensive. Granulation tissue formation is needed to fill the wound gap, then there’s the aspect of wound contraction. The wound edges come closer toward the center through contraction that reduces the size of the gap. The contraction is caused by myofibroblasts, which are like modified fibroblasts that are derived from pericytes, which have the ability to contract.

Healing tissues

Connective tissue healing is prolonged because of a limited blood supply. Bone, or osseous tissue, has great regeneration abilities because of osteoblasts that are held in reserve, which work with osteoclasts to remodel bones. Tendons and ligaments can jusually recover from injury, but a bad injury can result in scar tissue or rough surface that causes weaker tensile strength or function. Cartilage heals by fibrous repair. Adipose tissue can’t go through mitosis, but precursor cells differentiate to produce new tissue.

Epithelial tissue can regenerate easily enough. They are frequently subject to injury. Regeneration will occur if epithelium damage is superficial. It can’t happen, however, if the basement membrane or intercellular matrix is disrupted, so in these cases fibroblasts will repair with scar tissue.

Glandular tissues are pretty stable and when injured they simply regenerate new tissue. For example, liver can regenerate very well. But if there’s serious damage, then there might be some functional loss.

Nervous tissue is made up of neurons that can’t go through mitosis, so if they’re damaged, then they’re replase by gliosis or proliferation of neuroglia. The neuroglia create a scarlike mass to block damaged axons to grow any further. Peripheral nervous system can replace myelinated neurons if Schwann cells stay undamaged.

Muscle tissues are permanent, so when damaged there is only fibrous repair causing loss of function. But muscles have compensation capabilities. The muscle cells increase in size and strength, called hypertrophy, which is what you get when lifting weights.

Healing problems

Sometimes healing doesn’t go so well. If the damage is too much, then collagen causes an exaggeration in wound contraction process called contracture. This can create distortion, such as seen in disfiguration after serious skin burns.

A second problem are adhesions, which result from inflamed exudates between serous membranes. These cause restriction in movement such as after surgery of heart or lungs, which sometimes require patients to be readmitted due to complications.

Dhiscence is when a healing wound breaks open because of pressure on the tissues. This happens most commonly in the abdominal wall because pressure interferes with formation of maturing collagen. It can lead to violent episodes of coughing, vomiting or diarrhea. A deficiency of vitamin C could also cause dehiscence problems.

Keloids are masses of scar tissue that are protruding through skin. They happen when dermal collagen is overproduced. Proud flesh is a problem of excess granulation tissue. Suture complications can result in cases when keratin is sealed within a suture tract.

Lastly, therapy sometimes can interfere with healting as in radiation or chemicals used in cancer. And anti-inflammatory or immunosuppresants can stop protein synthesis, wound contraction and regeneration.

Controlling healing

Healing is regulated closely, but not well understood. We know of two categories of chemical control factors including growth factors and growth inhibitors. As their names imply, they act in antagonistic ways promoting growth and stopping it. They are vital for migration of fibroblasts and epithelial cells, as well as formation of blood vessels, mitosis, and collagen formation.

Healing depends on cell interactions, especially in the extracellular matrix. Receptors on fibroblasts allow for binding elements of intercellular material. So, the matrix plays a role in regeneration and repair. The matrix interactions provide the regulartory input for healing as long as it is available undamaged.

Somehow, contact between cells physically regulates mitosis. In other words, cells undergoing mitosis stop once contact inhibition happens. You can see this in cells growing in laboratories. They start dividing and migrate, but when they meet they stop.

Worth noting is that growth factor therapy is being studied to better control healing in the future. Preparations of various growth factors could be used for therapy in several instances. Such as burn victims.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

How cell injury happens and what is the result?

A normal cell has a general organization at a chemical level that involves atoms, molecules moving around in complex fashion that ultimately is critical to the way we live. The cell membrane and various organelles such as the mitochondria all have vital roles to play.


At the cellular level, injury is a result of three basic causes: deficiency, intoxication, or trauma. A deficiency is when the cell lacks a compound of a sort that causes interference with function such as when there’s a dietary deficiency of B vitamins. Intoxication is when a compound present actually poisons the cell, interfering with function such as when a biological infection, or toxic product in the cell like barbiturates. Trauma is when there is actual physical injury to the cell, causing loss of cell integrity such as hypothermia causing ice crystals or hyperthermia causing denaturation of cellular proteins.

The cell can respond in various ways by adapting with reversible (functional or structural) and, sometimes, irreversible (structural or deadly) changes.

The reversible may include alternative metabolisms such as in hypoxia when the cell changes from oxidative phosphorylation to glycolysis, or with altered size as in hypertrophy when demand increases. Reversible changes also include apoptosis that reduces cell numbers, production of cell-stress proteins (like heat stress or heat shock proteins) or organelle changes to make certain enzymes available as in detoxification.

There are also fatty changes as in the liver, residual bodies that are derived from phagosomes when lysosomes aren’t enough, and hyaline changes when proteins accumulate in a cell.

Structural reversible changes include blebs that project out of a cell and myelin figures that are membrane structural abnormalities.

Irreversible injury to cells involve unrecoverable structural changes to the cell membrane causing increased permeability or spillage. It can also involve similar changes to mitochondrial membranes or the structure of other organelles.

Cell death is an irreversible injury called necrosis. Unlike apoptosis, it’s not programmed. It can happen due to coagulation, when proteins are denatured quickly because of acid, heat or enzymes. Caseous necrosis happens as a type of coagulation necrosis in tuberculosis causing a cheeselike appearance. Gangrenous necrosis is another kind that happens when toxic metabolites of bacteria cause reduced blood flow and produce putrefaction.

If coagulation doesn't occur, and tissue breaks down quickly because of lysosomal enzymes then liquefaction necrosis has resulted.

Calcification is a deposition of calcium crystals at sites of necrosis. It occurs when cell injury allows calcium into the cell condensing in mitochondria and causing death. The calcium crystals can start out tiny, but become large masses in a process called dystrophic calcification.

And, when calcium is deposited only as a result of excessive calcium, as in hypercalcemia, then metastatic calcification has occurred. Generally, metatstatic calcium deposits are not severe, but can interfere with lung or kidney function.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

The basics of health and disease

What does healthy mean? Some would call it the absence of disease, or when a person can fully use all of his or her physical or mental capacities. But when what we understand as the concept of health is disrupted, in some way or another (which happens inevitably), we call it disease.


The study of the cause of this disease is what we call etiology and the field of etiological study can be specific, as in viral etiology or genetic etiology. Or, when the etiology of a disease is unknown, then idiopathic.

Unlike genetic etiology (think cystic fibrosis), which comes with a genetic structural or functional defect, congenital etiology has to do with factors affecting an embryo’s development in utero (think fetal alcohol syndrome).

The largest category of etiology is acquired disease. These are diseases that develop despite normal genes and embryonic development. Think everything else from tuberculosis to flu, to heart disease and cancer.

Diseases come with symptoms, signs or both. Signs are what is observable by another person – like clammy hands, fever, or irregular pulse. Symptoms are those that are found through physical examination with lab tests, x-rays, surgery.

When there’s a combination of signs and symptoms associated with a disease, we call it a syndrome (as in metabolic syndrome, Down’s syndrome).

After an examination of signs and symptoms, the pattern of development of the disease is pathogenesis. The pathogenesis could describer some kind of initial impact that produced the disease. The resulting condition is a sequela. If the pathogenesis had a rapid onset, it’s acute, and if it develops over time of months or years, then it’s chronic. When pathogenesis involves minor changes, the onset is said to be insidious.

The diagnosis, or identification, of a disease happens (or should happen) after a complete analysis of signs and symptoms with pathogenesis explained. Then, therapy follows with the goal of curing or reducing a patient’s signs or symptoms. The prognosis is the analysis of how a body responds to the therapy.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

What is inflammation?

Inflammation is a normal response of the body that involves an increase of blood flow to a site of injury. The signs of inflammation are redness (rubor), heat (calor), swelling (tumor) and pain (dolor). One other classic sign is loss of function (function laesa).


Acute inflammation is a dramatic localized response to injury. It comes vascular changes increasing blood flow (hyperemia) to the area that cause the redness and warmth as observed along with swelling. There’s also a cellular component, in which large numbers of white blood cells move to the injury to stop infectious agents and clear debris. The cells that come form what is referred to as an exudates.

Chronic inflammation is when inflammation lasts beyond six weeks (subacute applies to inflammation beyond a week, but not lasting as long as six weeks). A chronic response can last months and years. It is essentially a “standoff” between an injury and the body’s defense. They resist each other, but neither is strong enough to beat the other down.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

What causes a fever?

When inflammation comes with a body temperature that is elevated above normal, we call it a fever or pyrexia. The change in temperature is not a defect, but an adjustment by the hypothalamus to a new set point. The set point is established in consequence of release of fever-producing factors called pyrogens, whether endogenous or exogenous. Endogenous pyrogens are produced upon stimulation of exogenous agents.

The fever is a response to infectious, toxic or immunologic disease or injury, at least in warm-blooded animals – although cold-blooded animals like lizards often treat themselves similarly by lying in the sun to raise body temperature.

The fever enhances functions of the immune system and phagocytosis. Also, there are a few bacteria and viruses that reproduce more slowly in the heated temperature because of possible interference with uptake of iron.

So, our initial idea of a fever as something to treat may actually be our bodies’ ways of treating themselves to some kind of moderate degree. But antibiotics are a modern intervention that have given us the capacity to thwart the need of suffering through a fever.

Besides, a fever can actually cause damage itself as in the brain or in pregnancy. The excess heat can cause hyperthermia that creates cranial pressure or can harm a fetus, respectively.

Antipyretic therapy, such as with acetylsalicylic acid, is the way to go. They inhibit prostaglandin production in they hypothalamus, which results in a block of the set point elevation and returns temperature to a normal level.

But children with flu or measles shouldn’t take acetylsalicylic acid because of association with Reyes syndrome, so ibuprofen or something else should be used for children.

Reference

Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

Getting high off endorphins

I used to listen to this incredibly motivated motivational speaker years ago who was always talking about how you need to exercise daily to "release endorphins". The endorphins would make you high. Then you'd feel completely fantastic. And all your greatest creative ideas would enter your brain.

What the heck are these endorphins anyway? Well, they are your body’s own natural painkillers (1) and they are distributed throughout the brain stem binding to receptors. The drug, morphine, attaches to the same receptors to dull pain (1). The name endorphin, in fact, comes from “endogenous morphinelike substance” (1).

So, what about exercise? Anything to it? Yes. I was able to find in quite a few studies that exercise, almost any kind, does increase endorphin levels in the blood (2-7). In fact, a study in 1995 showed that when compared to meditation, running was more effective for releasing endorphins (7).To get the most potent pain-killing buzz from your workout, do high-intensity exercise to reach your anaerobic threshold. Anaerobic exercise promotes greater endorphin release than aerobic exercise (2). (Although the workout might come back to haunt you with pain later.) It was thought that lactic acid played a role in causing endorphin release, but this theory has been challenged (8).

Also, you don’t have to exercise for natural pain relief. There are other ways. Exposure to cold appears to stimulate endorphin release and a huge amount of electrical impulses to the brain (9). This led to one hypothesis that taking a cold shower daily may be useful to help those with depression (9). Electroacupuncture can help stimulate endorphin release, which may explain why it may be a good complementary treatment for pain (10).Massage therapy is also thought to stimulate endorphin release, but its effects are not proven (2).

It’s worth noting that in patients with heart failure, a functional disability includes decreased release of endorphins during exercise (11).

Reference List
1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
2. Bender T, Nagy G, Barna I, Tefner I, Kadas E, Geher P. The effect of physical therapy on beta-endorphin levels. Eur J Appl Physiol 2007;100:371-82.
3. Armstrong DW, III, Hatfield BD. Hormonal responses to opioid receptor blockade: during rest and exercise in cold and hot environments. Eur J Appl Physiol 2006;97:43-51.
4. Harbach H, Hell K, Gramsch C, Katz N, Hempelmann G, Teschemacher H. Beta-endorphin (1-31) in the plasma of male volunteers undergoing physical exercise. Psychoneuroendocrinology 2000;25:551-62.
5. Jarmukli NF, Ahn J, Iranmanesh A, Russell DC. Effect of raised plasma beta endorphin concentrations on peripheral pain and angina thresholds in patients with stable angina. Heart 1999;82:204-9.
6. Goldfarb AH, Jamurtas AZ. Beta-endorphin response to exercise. An update. Sports Med 1997;24:8-16.
7. Harte JL, Eifert GH, Smith R. The effects of running and meditation on beta-endorphin, corticotropin-releasing hormone and cortisol in plasma, and on mood. Biol Psychol 1995;40:251-65.
8. Petrides JS, Deuster PA, Mueller GP. Lactic acid does not directly activate hypothalamic-pituitary corticotroph function. Proc Soc Exp Biol Med 1999;220:100-5.
9. Shevchuk NA. Adapted cold shower as a potential treatment for depression. Med Hypotheses 2008;70:995-1001.
10. Lee SH, Lee BC. Electroacupuncture relieves pain in men with chronic prostatitis/chronic pelvic pain syndrome: three-arm randomized trial. Urology 2009;73:1036-41.
11. Perna GP, Modoni S, Valle G, Stanislao M, Loperfido F. Plasma beta-endorphin response to exercise in patients with congestive heart failure. Chest 1997;111:19-22.

Alternative treatment for Parkinson's

How is it that a traditional Ayurvedic medicine like Mucuna pruriens can be more effective than regular synthetic levodopa for Parkinson’s?

Many reasons, apparently. The botanical with natural L-DOPA appears to actually help restore endogenous levels of endogenous levodopa, dopamine, norepinephrine and serotonin in the substantia nigra (1). And, unlike synthetic levodapa, it doesn’t produce DNA damage (2). The neuroprotective effects are thought to come from copper-chelation properties (2). One clinical trial on 60 patients with Parkinson’s disease taking Mucuna pruriens reported that adverse effects were limited to only gastrointestinal issues, not lab reports (3).

Reference List

1. Manyam BV, Dhanasekaran M, Hare TA. Neuroprotective effects of the antiparkinson drug Mucuna pruriens. Phytother Res 2004;18:706-12.
2. Tharakan B, Dhanasekaran M, Mize-Berge J, Manyam BV. Anti-Parkinson botanical Mucuna pruriens prevents levodopa induced plasmid and genomic DNA damage. Phytother Res 2007;21:1124-6.
3. An alternative medicine treatment for Parkinson's disease: results of a multicenter clinical trial. HP-200 in Parkinson's Disease Study Group. J Altern Complement Med 1995;1:249-55.

It's finals week and you've got a tension headache

Got a tension headache? Don’t want to take an analgesic like aspirin or acetaminophen? You might try electroacupuncture. Sound like something out of sci-fi novel? Electroacupuncture is used widely in China; it’s just like acupuncture, but in which the needles deliver electrical pulses between therm. And according to a randomized, controlled, crossover trial in 2004, it can provide some effective relief for a tension headache, albeit only short-term (1).

Get headaches way too often? You might as well take poison. No, seriously! The same neurotoxic dinoflagellate contaminant that produces shellfish poisoning, and even botulinum toxin, could be injected to impede nerve impulse causing headache pain to provide significant relief (2-4).

Reference List
1. Xue CC, Dong L, Polus B et al. Electroacupuncture for tension-type headache on distal acupoints only: a randomized, controlled, crossover trial. Headache 2004;44:333-41.
2. Lattes K, Venegas P, Lagos N et al. Local infiltration of gonyautoxin is safe and effective in treatment of chronic tension-type headache. Neurol Res 2009;31:228-33.
3. de Ru JA, Buwalda J. Botulinum toxin A injection into corrugator muscle for frontally localised chronic daily headache or chronic tension-type headache. J Laryngol Otol 2009;123:412-7.
4. Freund BJ, Schwartz M. Relief of tension-type headache symptoms in subjects with temporomandibular disorders treated with botulinum toxin-A. Headache 2002;42:1033-7.

Levels of consciousness (and no, I'm not Deepak Chopra)

Odd as it is to measure something like consciousness, it is a must to determine a possible medical condition, and the levels must be precise to give an accurate status before and after treatment (1). A state of consciousness can indicate a person’s wakefulness, awareness and alertness (2). Consciousness may “lower” a level or more depending on a range of factors that include alcohol or barbiturate overdose, stroke, epilepsy, bacterial meningitis, diabetes, kidney failure or heart disease (1).

Example of consciousness terminology (1):

• Normal consciousness is characterized by a fully responsive, self-awareness and awareness of surroundings
• Inattention is when a patient finds it difficult to identify and attend revelant stimuli
• Confusion happens when thinking is slower or less clear; or when a patient is distracted
• Clouding (obtundation) is when inattention and confusion are more profound; rousing is more difficult
• Stupor is physical and mental activity at its minimum (kind of like me in the morning); you have to use persistent and vigorous stimulation to arouse them
• Coma is when a patient simply can’t be aroused, but might produce a pattern of behavior if stimulus is intense
  

Many clinical methods of have been used to determine the conscious state. The Glasgow Coma Scale, introduced in 1974 (2), has been functional in many hospitals including Grady Memorial Hospital in Atlanta, Georgia, for 30 years (3). The scale is easy to use using eye, verbal and motor responses (1;3). But it does have many limitations because there is a tendency to skew scores depending on experience of examiners and their paradigms (2). New techniques for determining consciousness may come in the future. They may include new terminology and new scales (2;3).

Reference List

1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
2. Matis G, Birbilis T. The Glasgow Coma Scale--a brief review. Past, present, future. Acta Neurol Belg 2008;108:75-89.
3. Tindall S. 1990. Levels of Consciousness. Clinical Methods: The History, Physical, and Laboratory Examinations. Available at: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cm&part=A1731

Don't depend on Glasgow Coma Scale

The Glasgow Coma Scale is easy to use for almost anyone to determine the state of a head injury. It includes eye, verbal and motor responses (see http://en.wikipedia.org/wiki/Glasgow_Coma_Scale).

But it should be clear that it should not be the only test used. This was a hard lesson for the medics that treated Natasha Richardson after her skiing head injury (2). For this reason when my daughter fell off a scooter and hurt her head, her doctor suggested I take her to the hospital for a scan.

Reference
1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
2. Tremblant M. 2009. 911 Calls Show Urgency of Richardson Fall. CBS News. Available at: http://www.cbsnews.com/stories/2009/03/31/entertainment/main4906004.shtml

Neural tube defects may not be related to high sugar intake

High glycemic load was previously thought to increase risk of neural tube defects after California researchers found that there appeared to be an association with maternal diets high in sugar in their state (1). However, the more recent National Birth Defects Prevention Study has found that the association does not exist among national population and other regions in the country (1). It is unclear why this is the case (1).

Reference List

1. Shaw GM, Carmichael SL, Laurent C, Siega-Riz AM. Periconceptional glycaemic load and intake of sugars and their association with neural tube defects in offspring. Paediatr Perinat Epidemiol 2008;22:514-9.

Going senile

My grandfather has, more than once, left my stove on for hours until a pan burns and a cloud sets off the smoke alarm. The other day he forgot to turn off the faucet and flooded my bathroom. I fear I can’t leave him alone. He could hurt himself or he could burn down my house.

Dementia is a symptom used in a broad way to describe any loss of ordered neural function. It affects my grandfather as senility—its cause being his age of 82. It is a relief that my grandmother, just as old, does not show similar signs. And I just hope my parents don’t get it. I hope I don’t get it. Worst case scenario would be Alzheimer’s disease—the slow progression of dementia to the point that mental function is surrendered. If you happen to live with a parent or grandparent who is one of the 6 percent of the population that has Alzheimer’s, then, yes, I feel for you. My situation doesn’t come close.

Depending on the pathological cause, dementia can be reversible. If altered mental function is due to depression, impaired heart function, or anemia, it can be helped. We know now that Pick’s and Alzheimer’s disease are different because they affect the cerebral cortex.

Although symptoms may be indistinguishable to Alzheimer’s, Pick’s causes atrophy of the gyri, which at autopsy is called “walnut brain.” Alzheimer’s doesn’t just affect the cerebral cortex. It also affects the hippocampus, the amygdale and the basal nucleus of Meynert. This is because of widespread depletion of acetylcholine (and other chemicals) resulting from loss of cells in the nucleus of Meynert. Neurons called pyramidal cells die, their associated axons die and the brain loses its white matter. The gyri shrinks and ventricals expand worsening the atrophy.

The severity and progression of Alzheimer’s depends on three findings: 1) neurofibrillary tangles that encircle or displace the nucleus of pyramidal cells; 2) neuritic plaques that contain a cluster of neural processes filled with filaments; 3) amyloid precursor protein, which is normal in cells, but is elevated in the brains of patients with Alzheimer’s. Ten percent of cases are familial due to a gene that produces amyloid protein, which may be related to Down syndrome. Most of those with Down syndrome do develop Alzheimer’s if they live beyond 45. A mutation of another gene called APP may be related to early-onset Alzheimer’s. And research also has identified enzyme (secretases) abnormalities that may result in increased conversion of abnormal APP to amyloid beta protein.

No, there are no practical treatments for Alzheimer’s, unfortunately. Someday maybe we’ll have something to degrade amyloid protein. Elevated aluminum levels found in patients who’ve had Alzheimer’s raises concerns that those with a genetic predisposition shouldn’t use aluminum cookware or other products such as deodorants containing aluminum. To remove aluminum, chelating agents have been used to reverse symptoms. Another experimental treatment is tetrahydroaminoacridine to enhance memory, but may cause liver damage. Aspirin also appears to slow inflammation that is part of Alzheimer’s.Healthy diet and exercise as well as exercise of cognitive skills remain the most important ways to help slow the progression of dementia and Alzheimer’s.

Reference List

Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.

MS patients can look forward to stem cell therapy

Stem cell therapy may be the treatment of the future for severe multiple sclerosis patients. Swedish researchers reported last February that bone marrow stem cell transplantation was successful for treating severe multiple sclerosis (1).

The researchers found improvement in symptoms after testing the therapy for five years on nine patients with severe MS, ages between 9 and 34 (1). The therapy has been studied for a total of 15 years (1).

Reference List

1. Fagius J, Lundgren J, Oberg G. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler 2009;15:229-37.

Feel down in the dumps? Could be Alzheimer’s disease

Lack of motivation may serve as a diagnostic criteria for Alzheimer’s disease. According to a discussion during the European Alzheimer’s Disease Consortium earlier this month, the apathy may be caused by functional impairment (1). The researchers noted that reduced “goal-oriented behavior, goal-directed cognitive activity and emotions” must persist over time, thought to be “at least four weeks”.

Reference List

1. Robert P, Onyike CU, Leentjens AF et al. Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders. Eur Psychiatry 2009;24:98-104.