Pathophysiology of disease (III)

I started reading this book last year – here’s a post from back then. It’s a great book – it’s well written, I’m learning a lot. But on the flip-side the book is, and was, hard work to read – so when I was last reading it I simply decided at one point to put it away (temporarily?) because I couldn’t be arsed to do the work it took to actually finish this book (not even close – there’s a lot of stuff in there). I recently decided I should have another go at it, partially on account of having learned some relevant stuff in the meantime which might result in some of the chapters being perhaps a little easier for me to read; I never really read any chapters ‘cold’ – i.e. without knowing anything about the topic – but a few of the topics covered I didn’t know much about, and these were really hard to read. Knowing stuff like what’s in here, here, here, here, here, here, and here will help make the book easier for you to read and I don’t think this should be the first medical textbook you read.

When I ‘stopped reading’ I had gotten to chapter 7, which is about nervous system disorders. It’s a very long chapter, which was probably part of the reason why that was where I stopped. I’ve now finished this chapter, as well as chapter 8 on diseases of the skin, chapter 9 on pulmonary disease, and chapter 10 on heart disease. I’ve started reading chapter 11 on vascular disease – I’m almost half way through the book at this point. A chapter takes a significant amount of time to read and I can’t possibly cover all the stuff they talk about in these chapters here, but I’ve added some general remarks related to chapters 7-9 below. I may cover chapter 10 later.

The nervous system chapter is as mentioned quite long and it covers a lot of stuff; the way I see it, there’s more interesting stuff about how these things actually work in a quarter of this chapter alone than there is in Oliver Sacks entire book The Man Who Mistook His Wife for a Hat. You do not find sentences like the first one below in Sacks:

“The prefrontal cortex (Figure 7-9) generally refers to the areas 9, 10, 11, 12, 45, 46, and 47 of Broadmann on the superior and lateral surfaces of the frontal lobes and the anterior cingulate, parolfactory, and orbitofrontal cortex inferiorly and mesially. These regions are essential for orderly planning and sequencing of complex behaviors, attending to several stimuli or ideas simultaneously, concentrating and flexibly altering the focus of concentration, grasping the context and meaning of information, and controlling impulses, emotions, and thought sequences. Damage to the frontal lobes or connections to the caudate and dorsal medial nuclei of the thalamus cause the frontal lobe syndrome. Patients may suffer dramatic alterations in personality and conduct, while most sensorimotor functions remain intact.” (You may find this link to anatomical terms of location to be helpful)

The chapter as always covers first how things are supposed to work, what is going on in that system, and then it has some stuff about what happens when things go wrong. That said, the line drawn between the parts dealing with physiology and the parts dealing with pathophysiology felt more fluid to me in this chapter than it did in most chapters in this book. There’s an obvious reason for that: The neurological system handles a huge amount of specific types of activities, and subcomponents of this system are often highly specialized; so I thought it made a lot of sense for them to include a few remarks about ‘what might go wrong if this specific mechanism is impacted for some reason’ while talking about ‘how things generally work’, and I found remarks such as the one above quite helpful. Aside from frontal lobe syndrome they also talk along the way about e.g. various forms of hearing loss, vision problems and how they might be caused by neurological problems (and how different neurological problems may manifest in different ways – i.e., which type of vision loss you can expect will depend on which specific neurological pathway is damaged), anatomy of sensory loss while dealing with the somatosensory system, as well as how language might be impacted by damage to specific regions of the brain. To take a few examples. They naturally couldn’t possibly cover all neurological pathologies in detail in a chapter like this, so they don’t try to do this either; what they do instead is that in the latter half they select out a few neurological disorders which are then covered in some detail in order to illustrate some central themes. The disorders covered are motor neuron diseases (primarily ALS), Parkinson’s disease, Myasthenia Gravis, epilepsy, dementia and Alzheimer’s disease, and stroke.

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Chapter 8 deals with diseases of the skin. It’s a short chapter, much shorter than the neurology chapter, and I won’t talk too much about it. It spends a few pages talking about how skin works and how it normally looks like, then there’s an overview of skin diseases and how to classify them, and then there’s a section about the pathophysiology of selected skin diseases (psoriasis, lichen planus, erythema multiforme, bullous pemphigoid, and leukocytoplastic vasculitis). Here’s an observation from this chapter which I’d never thought about:

“Physicians interested in the skin learned decades ago that the accurate diagnosis and classification of the many patterns of dermatitis were dependent upon a standardized nomenclature for the description and documentation of rashes. […] To illustrate the importance of terminology, imagine trying to describe a patient’s condition over the phone to another physician. Talking about a “red raised rash” may truthfully describe the eruption in some sense, but the mental image evoked could be any one of dozens of skin diseases. As the describer, the only way to accurately portray an eruption is through the use of precisely defined terms.”

So how does one go about describing these things? Well, here’s the system they’ve come up with and apply:

“The most important types of primary lesions include macules and patches, papules and plaques, vesicles and bullae, postules and nodules. The terms macule and patch denote flat areas of discoloration, without any discernible change in texture. Macules are 1 cm or less in diameter, while patches exceed 1 cm in size. Papules and plaques are elevated, palpable skin lesions, in which the breadth of the lesion exceeds its thickness. A papule is small, 1 cm or less in diameter, while a plaque exceeds 1 cm in size. Vesicles and bullae are fluid-filled spaces within the skin. Vesicles are less than 1 cm in diameter, while bullae exceed 1 cm in size. A vesicle or bulla containing purulent fluid is known as a postule. A nodule is a solid, rounded skin lesion in which diameter and thickness are roughly equal.”

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Chapter 9 is about pulmonary disease. I assume these Khan Academy videos cover stuff similar to what’s covered in the beginning of the chapter (I’ve seen all the videos about gas exchange aside from the last one, but I’ve only seen the last one in the introduction section so I don’t really know in detail what’s covered in the first ones) – at least I’ll say having watched some of these beforehand was helpful. The first part of the chapter talks about the normal structure of the lungs, basic anatomical features, static properties like compliance and elastic recoil as well as dynamic properties related to flow and resistance (I watched the fluid dynamics videos on Khan Academy a while back so some of this stuff was review), how matching of ventilation and perfusion is achieved (and what happens when there’s a mismatch between the two), and how breathing is controlled. The second part deals with the pathophysiology of some specific lung diases; asthma, COPD (treatment split up into two parts, dealing with chronic bronchitis and emphysema separately), idiopathic pulmonary fibrosis, pulmonary edema, and pulmonary embolism. Some observations from the chapter:

“At rest, the lungs take 4 L/min of air and 5 L/min of blood, direct them within 0.2 µm of each other, and then return both to their respective pools. With maximal exercise, flow may increase to 100 L/min of ventilation and 25 L/min of cardiac output. The lungs thereby perform their primary physiologic function of making oxygen available to the tissues for metabolism and removing the major by-product of that metabolism, carbon dioxide. The lungs perform this task largely free of conscious control, all the while maintaining PaCO2 within 5% tolerance. It is a magnificent feat of evolutionary plumbing and neural control. […] The amount of energy needed to maintain the respiratory muscles during quiet breathing is small, approximately 2% of basal oxygen consumption. Increasing ventilation in normal humans consumes relatively little oxygen until ventilation approaches 70 L/min. In patients with lung disease, the energy requirements are greater at rest and increase dramatically with exercise. Patients with emphysema may not be able to increase their ventilation by more than a factor of 2 because the oxygen cost of breathing exceeds the additional oxygen made available for the body.”

“The functional role of the lungs is to place ambient air in close proximity to circulating blood to permit gas exchange by simple diffusion. To accomplish this, air and blood flow must be directed to the same place at the same time. In other words, ventilation and perfusion must be matched. A failure to match ventilation to perfusion […] lies behind most abnormalities in O₂ and CO₂ exchange.”

“All blood vessels leak. In the adult human, leakage from the pulmonary circulation represents less than 0.01% of pulmonary blood flow, or a baseline filtration of approximately 10-20 mL/h. […] Pulmonary edema occurs when the transmural pressure is excessive for a given capillary permeability. […] in the presence of damaged capillary endothelium, small increases in otherwise normal transmural pressure may cause large increases in edema formation. Similarly, if the alveolar epithelial barrier is damaged, even the baseline filtration across an intact endothelium may cause alveolar flooding.”

“The English word “embolus” derives from a Greek root meaning “plug” or “stopper.” A pulmonary embolus consists of material that gains access to the venous system and then to the pulmonary circulation. Eventually, it reaches a vessel whose caliber is too small to permit free passage, and there it forms a plug, occluding the lumen and obstructing perfusion. […] It is a normal function of the pulmonary microcirculation to remove venous emboli. The lungs possess both excess functional capacity and a redundant vascular supply, making them a superb filter for preventing small thrombi and platelet aggregates from gaining access to the systemic circulation. However, large thromboemboli – or an accumulation of smaller ones – can cause substantial impairment of cardiac and respiratory function, including death. […] Pulmonary thromboemboli are quite common and cause significant morbidity. They are found at autopsy in 25-50% of hospitalized patients [my emphasis, US] and are considered a major contributing cause of death in a third of those. However, the diagnosis is made antemortem in only 10-20% of cases. […] More than 95% of pulmonary thromboemboli arise from thrombi in the deep veins of the lower extremity: the popliteal, femoral, and iliac veins. […] The most prevalent risk factor in hospitalized patients is stasis from immobilization, especially in those undergoing surgical procedures. The incidence of calf vein thrombosis in patients who do not receive heparin prophylaxis following total knee replacement is reported to be as high as 84%; it is more than 50% following hip surgery or prostatectomy. The risk of fatal pulmonary thromboembolism in these patients may be as high as 5%. […] The most devastating and feared complication of acute thromboembolism is sudden occlusion of the pulmonary outflow tract, reducing cardiac output to zero and causing immediate cardiovascular collapse and death. Large emboli that do not completely occlude vessels, particularly in patients with compromised cardiac function, may cause an acute increase in pulmonary vascular resistance. This leads to acute right ventricular strain and a fatal fall in cardiac output. Such dramatic presentations represent less than 5% of cases and are essentially untreatable. They serve to highlight the importance of primary prevention of venous thrombosis.”