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Diabetes and Kidney Failure

I wish my parents played Mozart when I was asleep because half the time I don't even know what the heck anyone's talking about!

I wish my parents played Mozart when I was asleep because half the time I don’t even know what the heck anyone’s talking about!

I don’t really think I’m that thick a guy (despite plenty of evidence to the contrary), but I do often encounter these blocks where I just don’t know what’s going on.

Most recently, it was in preparing to discuss the digestive system and how the pancreas participates in both the production of enzymes to digest food (Pancreatic Juice contains trypsin, chymotrypsin, elastase, etc) as well as hormones to aid the body in dealing with the coming wave of nutrients in the blood (i.e. how insulin and glucagon mediate blood glucose homeostasis).

The next unit we were getting into was the renal system – and in having our introductory discussion about the kidneys and their functions, the topic of kidney failure came up. That quickly led to a segue into diabetes (recalling the digestive system) and how many diabetics end up requiring dialysis due to chronic kidney failure.

‘So what’s the connection? Why do diabetics get kidney disease so often?’

I thought I knew – then, as my mouth started to open – I realized that I didn’t. I closed my mouth.

I think I asked my students to look into it, but … I couldn’t wait. So I jumped in.

diabetesFirst, a confirmation. A report from the 2007 US Department of Health and Human Services confirmed that not only is diabetes a common cause of kidney failure, it is the most common cause of kidney failure by a rather large margin.

Then, a quick reminder or the function of the kidney and the structure of its functional unit, the nephron – or which each kidney contains millions.

Briefly, the function of the kidney is to filter blood.

Peanut Gallery: ‘I thought the spleen did that!’

-well, the spleen does do that. But for an entirely different purpose. The spleen filters the blood for foreign particles, etc. as a function of the immune system. Lymph nodes filter the lymph for any foreign material brought back to the circulatory system as ‘run-off’, the spleen filters blood as it circulates through the body.

The Kidney also filters blood, but it does so in order to remove waste products that will otherwise build up and become toxic to the person / animal.

The way it does this filtration is by using a glomerulus. The glomerulus is a knot of capillaries with porous epithelia. The pores are large enough to permit the passage of water and other small molecules (urea), but small enough so that larger proteins and cells won’t leave the blood. Whatever material does filter through then either moves along and becomes urine, or is selectively reabsorbed into the blood.

Screen Shot 2015-03-25 at 4.13.48 PM

Awesome rendering of the glomerulus

The glomerulus looks a lot like this: (or at least it would if life were as cool as some people’s artistic impressions)

This is where blood comes in, at relatively high pressure, and the small molecules and water are pushed through fenestrations (windows) in the capillaries so they can drain into the renal tubule. The combination of capillary epithelial cells, basement membrane, and podocytes (cells that sit upon the capillaries) altogether called the Glomerular Filtration Barrier.This is the place where kidney function can really take a hit if there’s a problem – and if this breaks, the whole thing is broken.

Not surprisingly, it’s the glomerulus that fails in diabetes. The question is, ‘why?’

One prevailing theory has been that diabetics have generally higher amounts of glucose in their blood and it is known that glucose levels too high and too low are both dangerous. So, it’s not too much of a stretch to suspect that this is somehow to blame. The resulting injury is therefore called diabetic nephropathy.

However, more recently, the podocytes have been investigated as possible culprits. Rather than glucose itself, work published in 2010 suggested that it was insulin signaling – not glucose- that was involved in the damage to cells. Podocytes do have an insulin receptor that is engaged when glucose levels are high enabling the cell to restructure its cytoskeleton in a way that helps the cells to withstand the increased glomerular pressure that comes with filtering post-meal blood (incidentally, high blood pressure is another cause of kidney failure).

‘Knockout’ mice which specifically lack this insulin receptor on these podocytes (but otherwise express insulin receptors appropriately) were shown to suffer kidney damage very similar to that seen in diabetic nephropathy. Importantly, this damage occurred despite animals being otherwise normal (i.e. no abnormally high level of glucose in the blood). To be clear, without the insulin receptor, podocytes were unable to remodel cytoskeleton following meals, this lack of remodeling led to damage to the structure.

These results are also consistent with other animal models of diabetes (type I and type II) that exhibit a failure in glomerular insulin signaling early on in kidney disease.

Because these podocytes are terminally differentiated cells, they do not renew following damage meaning that kidney disease of this sort does not improve, but only progressively worsens.

This gives us a model that looks something like this

(ps – if anyone with deeper knowledge of this field reads this, I would certainly appreciate corrections)

Model

 
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Posted by on March 25, 2015 in Uncategorized

 

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Invitation to Submit Questions for Microbiology (Mini) Exam II

infectious_diseaseMy microbiology class is having a special mini-exam on the Tuesday after we come back from Spring Break. This exam will cover chapters 11 and 12 of the Cowen Microbiology text, which is basically ‘how do we kill microbes outside of the body’ and ‘how do we kill microbes inside the body?’ This exam will also have elements taken directly from Exam I presented as an opportunity to retain that material and be sure that we keep these core ideas in mind.

That said, I will be happy to entertain any questions proposed by students (or non-students) on these topics.

 
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Posted by on March 12, 2015 in Uncategorized

 

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Great Animation Outlining the Development of the GI tract

I’ve just found this amazingly well done video of the embryonic formation of the GI tract. I would recommend that my students watch it and concentrate simply on how the structures connect and how they get from a simple tube (shortly after conception) to their form in a fully developed human (i.e. baby -> adults).

Ultimately, this is just a review of basic anatomy. But a damn good one.

 
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Posted by on March 9, 2015 in Uncategorized

 

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It’s my emotional support animal… I have a letter.

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click the llama

 
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Posted by on March 6, 2015 in Uncategorized

 

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Invitation to Submit Questions for Respiratory Unit

As I’ve been doing lately, I wanted to offer the opportunity to my students (and anyone else who would like to) to submit questions for the Respiratory Unit Exam of my Pathophysiology class. Topics covered on this exam will focus primarily on the outline below. However, I wish to remind students that they are responsible for all the material covered in chapters 21-23 of Porth’s Essentials of Pathophysiology.

Airways preserved in the right lung, airways and pulmonary circulation in the left lung.

Airways preserved in the right lung, airways and pulmonary circulation in the left lung.

To submit questions, please provide a fully worked out multiple choice question in the comments section below. Also indicate the correct answer.

Respiratory Pathophysiology Outline (Please, forgive the formatting below, I’m having trouble fixing this appropriately in the browser):

  1. Control of Respiratory Function
    1. Conducting Airways
      1. Nasopharynx
      2. Larynx
  • Trachea
  1. Bronchial Tree (Primary -> Terminal)
  1. Respiratory Tissue (Acini)
    1. Respiratory Bronchiole
    2. Alveoli
      1. Type I, Type II Alveolar Cells and Alveolar macrophages
    3. Pulmonary (And Bronchial) Circulation
    4. Pleura
    5. Ventilation and the Mechanics of Breathing
      1. Chest Cage and Respiratory Muscles
      2. Lung Compliance
    6. Lung Volumes and Capacities
      1. Total Lung Capacity
      2. Tidal Volume
  • Etc.
  1. Diffusion according to Fick’s Law
  2. Oxygen Delivery
    1. Oxygen / Globin Dissociation Curves
  3. Infections
    1. The Common Cold
      1. Caused by a number of different viruses
      2. A number of different serotypes
    2. Influenza
      1. One of the most deadly uncontrolled human infections
      2. Three types of influenza (A,B, and C – A is most diverse)
        1. Influenza A
          1. Distinguished by serotypes based on H&N genes
  • Three types of infections
    1. Uncomplicated upper respiratory disease
    2. Viral Pneumonia
    3. Viral Pneumonia + Bacterial Pneumonia
  1. Pneumonia
    1. Typical*
      1. Bacterial ( pneumoniae)
    2. Atypical*
      1. Viral (Influenza, Chickenpox), Fungal, protozoan
  • Legionnaire’s Disease
    1. (I find that pneumonia caused by Legionella is placed as either typical or atypical depending on the source)
  1. Fungal Infections
  2. Tuberculosis
    1. Diagnosis
    2. Treatment
  3. Congenital and Acquired Obstructive Disorders
    1. CF
    2. Asthma
    3. COPD
    4. Pulmonary Hypertension – causes and outcomes

*The distinction between Typical and Atypical pneumonia appears to be more historic than clinically valuable. For this reason, on our exam we will continue to call S. pneumoniae the most common form of ‘Typical’ pneumonia, but otherwise not use these terms.

 
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Posted by on March 4, 2015 in Uncategorized

 

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The Digestive System

For a nice, easy introduction to the digestive system, Khan Academy has a video that I wish I had made myself (or at least written):


The digestive system: Hank takes us through the bowels of the human digestive system and explains why it’s all about surface area.

https://www.khanacademy.org/embed_video?v=qF6TBRaE2_A

For a little deeper understanding, Marion Diamond does a great job, but over a lot longer time (three lectures)

and, finally, if you want to check out the Magic School Bus episode that Marion Diamond was consulted on and then refused to be a part of because it didn’t have the guts to finish the ride through the digestive tract, check it out here:

 
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Posted by on March 2, 2015 in Uncategorized

 

UPenn Webinar – ‘Mickey’s Got Measles’

mickey-mouse-and-measles

Poor Mickey

Today, I attended the webinar, Mickey’s Got Measles, through the Live Faculty Lecture Series offered at the University of Pennsylvania. Today’s lecture focussed on the epidemiology of Measles, Herd Immunity, and Trends in Immunization was presented by Alison Buttenheim. Given the recent outbreak of Measles that puts 2015 well ahead of year-to-date infection numbers, it was very timely and an excellent lecture. If you have 50 minutes, I highly recommend that you check it out here.

 
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Posted by on February 27, 2015 in Uncategorized

 

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