NEET MDS Lessons
General Pathology
Aneurysm
An aneurysm is a localized abnormal dilation of a blood vessel or the heart
Types:
1. True aneurysm - it involves all three layers of the arterial wall (intima, media, and adventitia) or the attenuated wall of the heart.
e.g. Atherosclerotic, syphilitic, and congenital aneurysms, and ventricular aneurysms that follow transmural myocardial infarctions.
2 False aneurysm
(also called pseudo-aneurysm) is a breach in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space ("pulsating hematoma").
E.g. ventricular ruptures after MI that are contained by a pericardial adhesion
E.g. a leak at the junction of a vascular graft with a natural artery.
Aneurysms are classified by macroscopic shape and size
Saccular aneurysms
spherical outpouchings (involving only a portion of the vessel wall, and often contain thrombi.
Fusiform aneurysms
diffuse, circumferential dilation of a long vascular segment;
they vary in diameter and length and can involve extensive portions of the aortic arch, abdominal aorta, or even the iliacs.
Aortic Aneurysm
The two most important causes are:
1- atherosclerosis : the most common cause
It causes thinning and weakening of the media. The intimal plaques compress the underlying media and also compromise nutrient and waste diffusion from the vascular lumen into the arterial wall. The media consequently undergoes degeneration and necrosis, thus allowing the dilation of the vessel
2- cystic medial degeneration of the arterial media. E.g. Marfan syndrome.
3- Other causes include: trauma, congenital defects (e.g., berry aneurysms), infections (mycotic aneurysms), systemic diseases, such as vasculitis.
Mycotic Aneurysm :
Infection of a major artery that weakens its wall is called a mycotic aneurysm
possible complications: thrombosis and rupture.
It can originate from:
(1) embolization of a septic thrombus, usually as a complication of infective endocarditis
(2) extension of an adjacent suppurative process;
(3) circulating organisms directly infecting the arterial wall
Mycotic AAAs are atherosclerotic lesions infected by lodging of circulating microorganisms in the wall
- e.g. bacteremia from a primary Salmonella gastroenteritis.
Abdominal Aortic Aneurysm
Atherosclerotic aneurysms occur most frequently in the abdominal aorta ,the common iliac arteries, the arch, and descending parts of the thoracic aorta can also be involved
Pathogenesis
AAA occurs more frequently in men and rarely develops before age 50.
Atherosclerosis is a major cause of AAA
hereditary defects in structural components of the aorta (e.g., defective fibrillin production in Marfan disease affects elastic tissue synthesis)
Morphology :
Usually positioned below the renal arteries and above the bifurcation of the aorta
AAA can be saccular or fusiform
as large as 15 cm in diameter, and as long as 25 cm.
Microscopically: atherosclerosis with destruction and thinning of the underlying aortic media
the aneurysm frequently contains a laminated mural thrombus
Syphilitic Aneurysm
Caused by The spirochetes T. pallidum
Tertiary stage of syphilis can cause obliterative endarteritis of the involve small vessels in any part of the body, including the vasa vasorum of the aorta
This results in ischemic medial injury, leading to aneurysmal dilation of the aorta and aortic annulus, and eventually valvular insufficiency.
valvular insufficiency and massive volume overload lead to hypertrophy of the left ventricle. The greatly enlarged hearts are sometimes called "cor bovinum" (cow's heart).
CLINICAL CONSEQUENCES
1. Rupture → massive potentially fatal hemorrhage
2. Obstruction of downstream vessel → tissue ischemic injury
3. Embolism → from atheroma or mural thrombus
4. Impingement and compression on an adjacent structure
5. Presentation as an abdominal mass
Joint pathology
1. Rheumatoid arthritis
a. Cause is autoimmune in nature.
b. More common in women aged 20 to 50.
c. Characterized by inflammation of the synovial membrane. Granulation tissue, known as pannus, will form in the synovium and expand over the articular cartilage. This causes the destruction of the underlying cartilage and results in fibrotic changes and ankylosis.
Scarring, contracture, and deformity of the joints may occur.
d. Clinical symptoms include swollen joints. It can affect any joint in the body.
2. Osteoarthritis
a. Most common arthritis.
b. Cause is unknown.
c. Higher incidence in women, usually after age 50.
d. Characterized by degeneration of the articular cartilage and the formation of osteophytes (bony spurs) at the margins of affected areas.
Clinical signs and symptoms include:
(1) Stiff and painful joints affecting joints in the hand (phalangeal joints) and weight-bearing joints.
(2) Heberden’s nodes—nodules at the distal interphalangeal joint.
(3) Bocard’s nodes—nodules at the proximal interphalangeal joint.
Str. Pneumoniae
Probably the most important streptococci. Primary cause of pneumonia. Usually are diplococci. Ste. pneumoniae are α-hemolytic and nutritionally fastidious. Often are normal flora.
Key virulence factor is the capsule polysaccharide which prevents phagocytosis. Other virulence factors include pneumococcal surface protein and α-hemolysin.
Major disease is pneumonia, usually following a viral respiratory infection. Characterized by fever, cough, purulent sputum. Bacteria infiltrates alveoli. PMN’s fill alveoli, but don’t cause necrosis. Also can cause meningitis, otitis, sinusitis.
There are vaccines against the capsule polysaccharide. Resistance to penicillin, cephalosporins, erythromycins, and fluoroquinalones is increasing.
Histopathological techniques
Histopathological examination studies tissues under the microscope. During this study, the pathologist looks for abnormal structures in the tissue. Tissues for histopathological examination are obtained by biopsy. Biopsy is a tissue sample from a living person to identify the disease. Biopsy can be either incisional or excisional.
Once the tissue is removed from the patient, it has to be immediately fixed by putting it into adequate amount of 10% Formaldehyde (10% formalin) before sending it to the pathologist.
The purpose of fixation is:
1. to prevent autolysis and bacterial decomposition and putrefaction
2. to coagulate the tissue to prevent loss of easily diffusible substances
3. to fortify the tissue against the deleterious effects of the various stages in the preparation of sections and tissue processing.
4. to leave the tissues in a condition which facilitates differential staining with dyes and other reagents.
Mycobacterium leprae
- tuberculoid type has intact cellular immunity
- forms granulomas and kill the organisms (very few present).
- evokes a positive lepromin skin test
- localized skin lesions that lack symmetry
- nerve involvement (organisms invade Schwann cells) that dominates the clinical picture and leads to skin anesthesia, muscle atrophy and autoamputation.
- lepromatous leprosy patients lack cellular immunity
- no granulomas
- organisms readily identified
- negative lepromin skin test
- Bacteremia disseminates to cooler areas like the digits.
- symmetrical, skin lesions that produce the classic leonine facies; biopsy reveals grentz zone in superficial dermis and then organisms in macrophages.
- neural involvement is a late feature of the disease.
- lepromin skin test is to determine host immunity; not a diagnostic test.
- treatment: dapsone + rifampin
Nephrotic Syndrome
The patient will present with a triad of symptoms:
- Proteinuria, i.e. >3g/24hr-3.5g/24 hr
- Hypoalbuminaemia, i.e. <30g/L
- Oedema
>80% of cases are due to glomerulonephritis. In this syndrome, there is damage to podocytes
Clinical signs
- Pitting oedema, particularly in the limbs and around the eyes; may also cause genital oedema and ascites.
- Possible hypertension
Causes
- Primary causes – these are diagnoses of exclusion that are only made if secondary causes cannot be found
o Minimal change disease (MCD)
o Focal segmental glomerulosclerosis
o Membranous nephropathy
- Secondary causes – note that these fall into the same three categories as above:
o Minimal change disease – Hep B, SLE, diabetes M, sarcoidosis, syphilis, malignancy
o Focal segmental glomerulosclerosis –HIV, obesity, diabetes M, hypertensive nephrosclerosis
o Minimal change disease –drugs, malignancy, particularly Hodgkin’s lymphoma
- Differential diagnoses include cardiac failure, i.e. increased JVP, pulmonary oedema and mild proteinuria, and liver disease, i.e. reduced serum albumin.
- The condition causes an increased susceptibility to infection – partly due to loss of immunoglobulin in the urine. Patients tend to be prone to streptococcus infection, as well as bacterial peritonitis and cellulitis.
- Nephrotic syndrome also increases the risk of thromboembolism and hyperlipidaemia.
- The former is due to an increase in the synthesis of clotting factors and to platelet abnormalities, and the latter is a result of increased synthesis of these by the liver to counteract reduced oncotic pressure.
Investigations
- These are the same as those carried out in GN.
- Also, check for cholesterol as part of confirming the presence of hyperlipidemia.
- Renal biopsy – order this for all adults. In children, because the main cause is minimal change GN, steroids are the first-line treatment. Therefore, in children, biopsy is necessary only if pharmaceutical intervention fails to improve the situation.
- The hypercoagulant state seen in the nephrotic syndrome can be a risk factor for renal vein thrombosis. This can present as loin pain, haematuria, palpable kidney and sudden deterioration in kidney function. This should be investigated with Doppler USS, MRI or even renal angiography.
- Once diagnosed, give warfarin for 3 to 6 months.
Management
- Generally, this involves treatment of the underlying condition which is usually GN. Therefore, fluid management and salt intake restriction are priorities. The patient is usually given furosemide along with an ACE inhibitor and/or an angiotensin II receptor antagonist. Prophylactic heparin is given if the patient is immobile. Hyperlipidaemia can be treated with a statin.
Nephritic Syndrome
Acute and chronic
forms of the syndrome exist. The main difference between this and nephrotic syndrome is that in nephritic syndrome haematuria is present. There is also proteinuria, hypertension, uraemia, and possibly oliguria. The two standout features are hypertension and RBC casts. The urine will often appear ‘smoky’ in colour due to the presence of RBC casts. Very rarely, it may appear red
Causes
1. Post-streptococcal
2. Primary:
- Membranous glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger’s disease)
3. Secondary
- HSP
- Vasculitis
Clinical Features
- Abrupt onset of :
o Glomerular haematuria (RBC casts or dysmorphic RBC)
o Non-nephrotic range proteinuria (< 2 g in 24 hrs)
o Oedema (periorbital, sacral )
o Hypertension
o Transient renal impairment (oliguria, uraemia)
- Urinary casts – these are cylindrical structures produced by the kidney and present in the urine in certain renal diseases. They form in the DCT and collecting duct, dislodging and passing in the urine where they are detected by microscopy. RBC casts are usually associated with nephritic syndrome. The presence of RBCs within a cast is always pathologic and strongly indicative of glomerular damage.
- The proteinuria present is often smaller than in nephrotic syndrome, thus a coexistent condition of nephrotic syndrome is not usually present.
- Encepelopathy may be present, particularly in children, due to electrolyte imbalances and hypertension. This type of presentation is indicative of glomerular damage, but requires renal biopsy to determine the exact problem. In this respect it is similar to nephrotic syndrome.
Overlapping of the two syndromes is possible as nephrotic syndrome may precede nephritic syndrome, although not vice-versa.
Mechanisms of the syndrome vary according to cause; both primary and secondary causes exist. Post-infectious GN is the classic illustration of nephritic syndrome, but the condition may be caused by other glomerulopathies and by systemic diseases such as connective tissue disorders
Two clinical terms to remember:
- Nephritic syndrome; which comprises edema, proteinuria, hypoalbuminemia, hematuria (smoky urine), oligurua and hypertension.
- Nephrotic syndrome; which comprises of albuminuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria.
Congestive heart failure (CHF)
A. Left-sided CHF
1. May result from nearly any heart disease affecting the left ventricle (e.g., ischemic heart disease, hypertension, valvular disease).
2. Common signs and symptoms include:
a. Dyspnea (shortness of breath) exacerbated by exertion.
b. Paroxysmal nocturnal dyspnea.
c. Orthopnea.
d. Tachypnea.
e. Pleural effusion.
f. Consequences include pulmonary edema.
B. Right-sided CHF
1. The most common cause of right heart failure is left heart failure. It uncommonly occurs in isolation. Other causes include left-sided lesions (mitral stenosis), pulmonary hypertension, cardiomyopathy, and tricuspid or pulmonary valvular disease.
2. Frequently presents with peripheral edema, especially in the ankles and feet (i.e., dependent edema), enlarged liver or spleen, and distention of the neck veins.