Radiculopathy

Heart block

Disease class: Cardiac conduction system disease

This is a cardiac arrhythmia.

 

Types

• Adams-Stokes syndrome
• Atrioventricular block 
• Bundle-branch block
• Interatrial block
• Sick sinus syndrome
• Sinoatrial block 

Diabetic nephropathy

Disease class: Kidney diseases

Diabetes mellitus 

This refers to kidney damage secondary to chronic hyperglycaemia. 

Essential hypertension

MeSH: Hypertension
ICD-11: Hypertensive diseases 

Essential hypertension refers to hypertension which is not caused by any known diseases (e.g. Glomerulonephritis).
This is one of the most common diseases in elderly patients.

 

Pathophysiology

The underlying mechanism behind this disease is unknown, but it becomes more prevalent with advanced age. It appears to reflect a gradual decline in the body's ability to self-regulate the blood pressure at an appropriate 'setting'.

 

Complications

Acute

• Cerebrovascular accident
• Hypertensive emergency

Chronic

• Hypertensive heart disease
• Hypertensive kidney disease
• Hypertensive retinopathy

Hypertensive retinopathy

MeSH disease class: Hypertension

 MeSH disease class: Retinal diseases

A common degenerative condition, caused by chronic uncontrolled hypertension.

Causes

• Essential hypertension
• Hypertensive emergency

Pathophysiology

• The pressure of the fluid in the circulatory system is too high.
• The forces transmitted by the circulating bloodstream to the vessels are high enough to cause vascular damage.
• Arterioles in the eyes become damaged and atherosclerosis develops. They thicken and shorten.
• Vessels rupture and haemorrhage into the eye.
• Areas of the retina become ischaemic and appear pale.

 

Signs on fundoscopy

Arteriolar changes

• Copper wire arterioles : The arterioles appear a bright metallic orange, like copper. The central light reflex is seen across part of the width of the arteriole.
• Silver wire arterioles : The arterioles appear a bright metallic white, like silver. The central light reflex is seen across the entire width of the arteriole.
• Arteriovenous (AV) nicking : The venules are by compressed by arterioles, as if they are being nicked or nipped. This appears as a point of tight constriction of a vein, with bulging of the vein on both sides of the constriction.
• Salus sign: At points of intersection with arterioles, the course of the venule is deflected and appears irregular. The venule is bent around the arteriole like a horseshoe bent around a stake. The course of the venule is deflected and appears irregular. This happens due to tension on the venule as the arteriole shortens.

Advanced retinopathy lesions

• Microaneurysms
• Blot hemorrhages 
• Flame hemorrhages
• Ischaemic changes (e.g. cotton wool spots)
• Hard exudates
• Optic disc oedema: Swelling of the optic disc
• Macular star: a ring of exudates around the retina

 

Grading

• Keith Wagener Barker (KWB) Grades 1-4

Eisenmenger's syndrome

Hypertensive renal disease

ICD-11: Hypertensive diseases 

Also known as

• Hypertensive kidney disease 

A common degenerative condition, caused by chronic uncontrolled hypertension.

 

Causes

• Essential hypertension
• Hypertensive emergency

 

Pathophysiology

• The pressure of the fluid in the circulatory system is too high.
• The forces transmitted by the circulating bloodstream to the vessels are high enough to cause vascular damage.
• Arterioles in the kidneys become damaged and atherosclerosis develops.
• Vessels rupture and haemorrhage into the renal parenchyma.

Amyotrophic lateral sclerosis

Disease class: Motor neuron disease

Disease class: Spinal cord diseases

 Disease class: TDP-43 proteinopathies

Also known as 

• ALS 
• Lou Gehrig's disease

Signs and symptoms

• Bulbar and pseudobulbar palsy

Diabetic retinopathy

Disease class: Retinal diseases

Diabetes mellitus 

This refers to retinal damage secondary to chronic hyperglycaemia.

Cirrhosis

Organ system: The digestive system

Organ: The liver

Disease class:  Liver diseases

Cirrhosis is a disease caused by long-term damage and fibrosis of the liver.
Functional hepatocytes are lost and the liver is unable to regenerate because the normal fibrotic architecture is lost and space is occupied by fibrosis.

It is a type of chronic liver disease. 

 

Causes  

• Chronic hepatitis
• Medications 
• Aflatoxin

 

Symptoms

• Gynaecomastia 
• Fatigue 
• Pruritus 

 

Signs

• Jaundice 
• Spider naevi
• Palmar erythema
• Nail clubbing 
• Dupuytren's contracture (alcohol related)
• Parotid enlargement (alcohol related)
• Peripheral neuropathy (alcohol related)
• Cerebellar signs (alcohol related)
• Hepatomegaly (alcohol related) (non-alcoholic fatty liver disease) (haemochromatosis)
• Hyperpigmentation (haemochromatosis)
• Kayser-Fleisher rings (Wilson's disease)

 

Complications

• Hepatic encephalopathy. Causing:
• Drowsiness
• Confusion
• Coma
• Metabolic flap (asterixis) (sign)
• Confusion
• Impaired excretion. Causing:
• Jaundice
• Itching (pruritus)
• Hypoalbuminaemia
• Ascites
• Peripheral oedema
• Leukonychia (sign)
•  Coagulopathy
• Easy bruising
• Haemorrhages
• Portal hypertension
• Ascites
• Oesophageal varices and bleeding
• Rectal varices and bleeding
• Caput Medusae (sign)
• Acid-base imbalance
• Respiratory compensation and alkalosis (sign)
• Hepatic encephalopathy
• Hepato-renal syndrome
• Hepatocellular carcinoma

 

Decompensation

Even a cirrhotic liver can compensate for the loss of functional liver tissue. However if the function of the liver is impaired for any reason, the patient may decompensate and rapidly develop life-threatening physiological abnormalities. As liver function becomes critically low the patient will experience these abnormalities more and more frequently.

 

Management 

This depends on the underlying cause and the consequences of the liver failure for this patient.

• Vitamin K. This allows the body to produce clotting factors as efficiently as possible, despite the liver pathology.  This helps to manage coagulopathy.

• Endoscopy and variceal banding

• Beta blockers
• Propranolol lowers the portal vein pressure, reducing portal hypertension. It also reduces renin secretion. This helps to reduce variceal bleeding and hepato-renal syndrome.
• Vasopressin analogues
• Terlipressin seems to be the most effective vasopressin treatment for hepato-renal syndrome.
• These have vasoconstrictive effects on the dilated splanchnic blood vessels. This reduces portal hypertension and improves variceal bleeding.
• This reduces sympathetic nervous system activity. There is an increase in glomerular filtration rate and deactivation of the vasoconstrictor and sodium-conserving hormones, particularly the renin-aldosterone system. There is reduced plasmsa renin activity, improving naturesis. This helps to reverse hepato-renal syndrome.

• TIPS: Transjugular Intrahepatic Portosystemic Shunt

Future management 

• Reversing liver cirrhosis

Intermittent claudication

Definition

Claudication is a cramp-like pain which occurs in the legs while walking. It may cause the sufferer to limp or stop them from walking entirely.
Intermittent claudication occurs when a person has to stop every so often to let the pain to subside. This is caused by the build-up of waste products in the muscles.

Source: Black's Medical Dictionary (42nd ed, 2010, ISBN 978-1-4081-0419-4)

 

Causes

• Peripheral arterial disease
• Thromboangiitis obliterans

Vascular dementia

Disease class: Cerebrovascular disorders

Disease class: Dementia

Disease class: Leukoencephalopathies

VD is the second most common cause of dementia. 

 

Pathophysiology

This is dementia caused by a series of small infarctions in the brain (strokes). Each infarction kills some neurons. With enough infarctions throughout the brain, the neuronal loss accumulates.

Symptoms

These patients often present with impaired cognition, impaired memory, and personality changes.

Prognosis

There may be a history of strokes (cerebrovascular infarctions). The disease progression is classically step-by-step, with dramatic deteriorations after each new infarction. It can appear to be a gradual decline in patients with very frequent, very small brain infarctions. It may develop over months or decades, but the changes are irreversible. 

Alzheimer disease

Disease class: Tauopathies

AD is the most common cause of dementia.

Pathophysiology

This disease has been poorly understood throughout medical history despite a large amount of research. There is an accumulation of tau protein. The protein "beta-amyloid" misfolds and accumulates in toxic plaques which can kill neurons. On brain scans, gross atrophy tends to appear first in the temporal lobes and parietal lobes. The hippocampus (in the medial temporal lobe) is usually one of the first structures affected. The hippocampus plays a key role in transferring short-term memories into long-term memory, and this is why anterograde amnesia is usually an early symptom.

Patients with Down's syndrome (tri-somy 21) have an 3rd copy of chromosome 21. Chromosome 21 contains the gene which produces beta-amyloid, therefore trisomy 21 patients have an unusually high amount of beta-amyloid in their brain. These patients have an extremely high rate of Alzheimer's disease, with an early onset.

Symptoms

These patients usually notice significant forgetfulness and disorientation as their first symptoms. Extrapyramidal symptoms usually develop late in the course of the disease.

Osteoarthritis

Disease class: Arthritis
Disease class: Rheumatic diseases 

Types

• osteoarthritis, Hip
• osteoarthritis, Knee
• osteoarthritis, Spine

This is a type of arthritis which is not caused by inflammatory processes.

 

Symptoms

• Chronic pain 
• Reduced mobility
• Joint locking
• Joint instability 
• Limited range of movement

 

Signs

• Crepitus
• Bouchard's nodes (proximal IP joint)
• Heberden's nodes (distal IP joint)

 

Investigations

Radiograph imaging

• Joint space narrowing
• Osteophyte development
• Subchondral sclerosis
• Subchondral cyst formation 
• Subluxation

 

Management

• Pain management
• Replacement arthroplasty

Peripheral vascular diseases

Disease class: Vascular diseases

Also known as PVD.

 

Types

• Blue toe syndrome
• Erythromelalgia
• Livedo reticularis
• May-Thurner syndrome
• Peripheral arterial disease
• Phlebitis
• Raynaud disease

Dementia

Disease class: Brain diseases 

Disease class: Neurocognitive disorders

 Definition

An acquired and irreversible deterioration in intellectual function.

Around 10 per cent of people aged over 65 and 20 per cent of those aged 75 or over are affected to some extent. The disorder is due to progressive brain disease. It appears gradually as a disturbance in problem-solving and agility of thought which may be considered to be due to tiredness, boredom or depression.

As memory failure develops, the affected person becomes bewildered, anxious and emotional when dealing with new surroundings and complex conversations.

 Source: Black's Medical Dictionary (42nd ed, 2010, ISBN 978-1-4081-0419-4) 

 

Pathophysiology

There is an accelerated rate of neuronal death, and so the amount of matter in the brain decreases significantly. In autopsies, the brain is clearly smaller and lighter.

Sketched illustration of serial CT scans.View: coronal. Left: patient with dementia. Center: same patient after 5 months. Right: patient with advanced dementia

On brain scans, the ventricles (fluid-filled spaces in the brain which act like a waste-removal system) appear larger because there is less brain matter around them. The gyri (folds of brain tissue) appear smaller. The sulci (valleys of empty space between gyri) appear wider. There is more empty space between the brain and the skull.

 

Symptoms

• Short-term memory impairment, forgetfulness 
• Cognitive impairment 
• Declining attention
• Depression 
• Sleep disturbances, insomnia
• Passivity, social withdrawal
• Emotional instability 
• Loss of orientation in time and space 
• Loss of spatial awareness and orientation
• Inappropriate social behaviour
• Worsening symptoms late in the evening (sundowning) 
• Aggression, physical violence 
• Hypersexual behaviour 
• Long-term memory impairment, loss of identity 
• Paranoia, delusional beliefs
• Hallucinations
• (Late stage) alogia (little or no speech)
• (Late stage) agitation, restlessness
• (Late stage) incontinence
• (Late stage) immobility
• (Late stage) dysphagia 
• (Late stage) progressive decline in appetite and thirst 
• (Late stage) increasing periods of sleep and unconsciousness 
• (Late stage) loss of autonomic regulation, extremities become cold

There is often a loss of fidelity of the personality. Spouses and family members of dementia patients often report that the patient seems to have become a different person.  

 

Causes of dementia

There are dozens of causes of dementia.

• Alzheimer's disease (AD): the most common cause of dementia.
• Vascular dementia: the second most common cause of dementia.
• Parkinson's disease: These patients usually present with extrapyramidal symptoms. Dementia usually develops late in the course of this disease.
• Parkinson-plus syndromes: This is a group of diseases with similar clinical patterns. These patients often present with extra-pyramidal symptoms and cognitive impairment. They develop dementia much earlier than patients with Parkinson's disease. Includes: 
• Dementia with Lewy bodies (DLB): DLB is the third most common cause of dementia.
• Multiple system atrophy (MSA)
• Progressive supranuclear palsy (PSP)
• Pick's disease
• Fronto-temporal dementia (FTD): This disease leads to preferential destruction of neurons in the frontal and temporal regions. Since the frontal lobe regulates social behaviour, these patients often present with personality changes and socially inappropriate behaviour.
• Normal pressure hydrocephalus (NPH). These patients classically present with incontinence, gait disturbances and dementia.
• Creutzfeldt-Jakob disease (CJD) is an infection which can bring a healthy young person to a state of dementia in a matter of months.

 

Pathophysiology

Sketched illustration of CT scans from 3 patients. View: axial. Left: NPH, Center: FTD, Right: DLB.

NPH: There is an imbalance between CSF production and resorption. Progressively larger volumes of CSF occupy a gradually expanding ventricular system. There is clear ventricular enlargement on the axial view.
FTD: The atrophy is significantly more advanced in the frontal lobes (top of the image). Notice the amount of empty space before the frontal lobes, and the width of the sulci there.
DLB: There is global atrophy with enlargement of the ventricles. The atrophy is not significantly more advanced in one particular lobe.

Parkinson's disease

Disease class: Neurodegenerative diseases

Disease class: Parkinsonian disorders

Also known as 

Hypokinetic rigid syndrome

 

Physiology

• The basal ganglia.

 

Pathophysiology

In a brain with Parkinson's disease, there is a death of cells in the substantia nigra (black substance). These cells are specialised in producing dopamine. Without them, the ability of the basal ganglia to produce sufficient dopamine is reduced, and the "unlocking" signal is too weak. This means that the inhibitory signals are not sufficiently deactivated, so there is too much inhibition.

Motor inhibition results in bradykinesia (slow movement), akinesia (no movement), resting tremor (rapidly alternating muscle contractions and relaxations), increased muscle tone (constant contraction and tension of all muscles), expressionless facies (lack of facial expression) and more. The motor symptoms are the most famous, as they are easy to recognise, and can progress to complete (but reversible) immobility. This is terrifying for patients, especially those living alone. However, the dysfunction of the basal ganglia affects many circuits, and a large range of neuropsychiatric symptoms often develop.

Many cognitive abilities are impaired including working memory, facial recognition, social inhibition. Sleep is commonly dysfunctional. Depression is common and hallucinations occur in 50%. The disease often results in dementia eventually.

It's not known why there is cell death in the substantia nigra neurons specifically, but there has been a wealth of research into the area. The remaining neurons in the brain of these patients often contain Lewy bodies (clumps of a protein called alpha-synuclein). Certain variants of the gene (SNCA) which encodes this protein have been linked to Parkinson's disease. Other genes associated with Parkinson's disease (such as LRRK2) also encode proteins found in the cytoplasm (cell contents) of neurons.

In a brain which has had destruction of basal ganglia: e.g. pallidotomy, thalamotomy, there is a reduction in inhibition. This reduces the symptoms of Parkinson's disease, but can also cause dyskinesia (purposeless involuntary movements) and ballismus (dramatic involuntary flailing movements of the limbs or face). Damage to the basal ganglia can also cause impaired processing of languages, visuospatial construction and other brain functions. Bilateral (both sided) destruction of basal ganglia components greatly increases the risk of dysfunction, potentially leading to unintelligible speech, apathy, depression and difficulty coordinating the muscles of the head (pseudobulbar palsy).

 

Management

Since inhibition of motor activity is the main concern for most of these patients, treatment is used which reduces the inhibition. Pro-drugs like levodopa (which the body converts to dopamine), and drugs which signal like dopamine (e.g. pramipexole, bromocriptine), can be used to enhance dopaminergic signalling levels in the brain. This helps the basal ganglia to reach the dopamine levels needed to unlock the basal ganglia.

The problem with these treatments is that the dopamine is not being released precisely. This results in dyskinesia (involuntary movements) from unnecessary inhibition of motor signals. Dopamine also has functions elsewhere in the brain, including the mesolimbic pathway. Adding dopamine to these systems can cause psychosis (loss of grasp on reality), impulsive behaviours (such as gambling, drug addiction, excessive spending) and punding (becoming fascinated in pointless activities like disassembling household objects and repeating the activity for hours). These are important side effects of Parkinson's disease treatments.

It's also important to note that dopamine has peripheral effects (the body), not just central effects (the brain). Levodopa is intended to affect the brain but not the peripheral nerves, so any patient given levodopa should be given a drug to block peripheral action (e.g. carbidopa).

In severe cases of Parkinson's disease, neurosurgeons can offer to destroy parts of the basal ganglia to achieve a reduction of inhibition. As described above, this can leave patients with lifelong dyskinesias such as ballismus, or even significant cognitive impairments.

[Hepatology] Chronic liver disease

Chronic liver disease refers to liver pathologies which last longer than 6 months.

The main chronic liver diseases are: 

• Chronic hepatitis
• Cirrhosis
• Malignancies

Progression

1. Chronic inflammatory stimuli (e.g. hepatitis viruses) maintain chronic hepatitis. 
2. Chronic hepatitis causes progressive fibrosis.
3. The fibrosis culminates in cirrhosis.
4. Cirrhosis provides a conducive environment for cellular transformation. 
5. This environment favours the development of hepatocellular carcinoma.