NEET MDS Lessons
General Pathology
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.
Hepatitis A virus.
- Hepatitis A (HAV) is a self-limited hepatitis caused by an RNA virus
- Symptoms last 2 to 4 weeks.
- There is no risk of developing chronic hepatitis in the future.
- Incubation period is short, lasting 2 to 6 weeks.
- Infection is identified by HAV-specific antibodies (IgM if acute, IgG if past disease).
- The usual route of infection is fecal-oral transmission by contaminated food. There is no carrier state and no chronic disease
- Laboratory diagnosis: ELISA test for IgM antibody.
- Vaccine: killed virus.
- Prevention: serum immunoglobulins are available.
Congenital heart defect
Congenital heart defects can be broadly categorised into two groups,
o acyanotic heart defects ('pink' babies) :
An acyanotic heart defect is any heart defect of a group of structural congenital heart defects, approximately 75% of all congenital heart defects.
It can be subdivided into two groups depending on whether there is shunting of the blood from the left vasculature to the right (left to right shunt) or no shunting at all.
Left to right shunting heart defects include
- ventricular septal defect or VSD (30% of all congenital heart defects),
- persistent ductus arteriosus or PDA,
- atrial septal defect or ASD,
- atrioventricular septal defect or AVSD.
Acyanotic heart defects without shunting include
- pulmonary stenosis, a narrowing of the pulmonary valve,
- aortic stenosis
- coarctation of the aorta.
cyanotic heart defects ('blue' babies).
obstructive heart defects
cyanotic heart defect is a group-type of congenital heart defect. These defects account for about 25% of all congenital heart defects. The patient appears blue, or cyanotic, due to deoxygenated blood in the systemic circulation. This occurs due to either a right to left or a bidirectional shunt, allowing significant proportions of the blood to bypass the pulmonary vascular bed; or lack of normal shunting, preventing oxygenated blood from exiting the cardiac-pulmonary system (as with transposition of the great arteries).
Defects in this group include
hypoplastic left heart syndrome,
tetralogy of Fallot,
transposition of the great arteries,
tricuspid atresia,
pulmonary atresia,
persistent truncus arteriosus.
Gout
This is a disorder caused by the tissue accumulation of excessive amounts of uric acid, an end product of purine metabolism. It is marked by recurrent episodes of acute arthritis, sometimes accompanied by the formation of large crystalline aggregates called tophi & chronic joint deformity. All of these are the result of precipitation of monosodium urate crystals from supersaturated body fluids. Not all individuals with hyperuricemia develop gout; this indicates that influences besides hyperuricemia contribute to the pathogenesis. Gout is divided into primary (90%) and secondary forms (10%).
Primary gout designates cases in whom the basic cause is unknown or when it is due to an inborn metabolic defect that causes hyperuricemia.
In secondary gout the cause of the hyperuricemia is known.
Pathologic features
The major morphologic manifestations of gout are
1. Acute arthritis
2. Chronic tophaceous arthritis
3. Tophi in various sites, and
4. Gouty nephropathy
Acute arthritis
- The synovium is edematous and congested,
- There is an intense infiltration of the synovium & synovial fluid by neutrophils.
- Long, slender, needle-shaped monosodium urate crystals are frequently found in the cytoplasm of the neutrophils as well as in small clusters in the synovium.
Chronic tophaceous arthritis:
- This evolves from repetitive precipitation of urate crystals during acute attacks. The urates can heavily encrust the articular surfaces and form visible deposits in the synovium.
- The synovium becomes hyperplastic, fibrotic, and thickened by inflammatory cells, forming a pannus that destroys the underlying cartilage, and leading to erosions of subjacent bone.
- In severe cases, fibrous or bony ankylosis occurs, resulting in loss of joint function.
Tophi
These are the pathognomonic hallmarks of gout.
- Tophi can appear in the articular cartilage, periarticular ligaments, tendons, and soft tissues, including the ear lobes. Superficial tophi can lead to large ulcerations of the overlying skin.
- Microscopically, they are formed by large aggregations of urate crystals surrounded by an intense inflammatory reaction of lymphocytes, macrophages, and foreign-body giant cells, attempting to engulf the masses of crystals.
Gouty nephropathy
- This refers to the renal complications associated with urate deposition including medullary tophi, intratubular precipitations and renal calculi. Secondary complications such as pyelonephritis can occur, especially when there is urinary obstruction.
Pathogenesis
- Although the cause of excessive uric acid biosynthesis in primary gout is unknown in most cases, rare patients have identifiable enzymatic defects or deficiencies that are associated with excess production of uric acid.
- In secondary gout, hyperuricemia can be caused by increased urate production (e.g., rapid cell lysis during chemotherapy for lymphoma or leukemia) or decreased excretion (chronic renal failure), or both. Reduced renal excretion may also be caused by drugs such as thiazide diuretics, because of their effects on uric acid tubular transport.
- Whatever the cause, increased levels of uric acid in the blood and other body fluids (e.g., synovium) lead to the precipitation of monosodium urate crystals. The precipitated crystals are chemotactic to neutrophils & macrophages through activation of complement components C3a and C5a fragments. This leads to a local accumulation of neutrophils and macrophages in the joints and synovial membranes to phagocytize the crystals. The activated neutrophils liberate destructive lysosomal enzymes. Macrophages participate in joint injury by secreting a variety of proinflammatory mediators such as IL-1, IL-6, and TNF. While intensifying the inflammatory response, these cytokines can also directly activate synovial cells and cartilage cells to release proteases (e.g., collagenases) that cause tissue injury.
- Repeated bouts of acute arthritis, however, can lead to the permanent damage seen in chronic tophaceous arthritis.
b Pseudogout (chondrocalcinosis) (Calcium pyrophosphate crystal deposition disease). Pseudogout typically first occurs in the age 50 years or older. It involves enzymes that lead to accumulation and eventual crystallization of pyrophosphate with calcium. The pathology in pseudogout involves the recruitment and activation of inflammatory cells, and is reminiscent of gout. The knees, followed by the wrists, elbows,
shoulders, and ankles, are most commonly affected. Approximately 50% of patients experience significant joint damage.
Infectious Arthritis can cause rapid joint destruction and permanent deformities. Microorganisms can lodge in joints during hematogenous dissemination, by direct inoculation or by contiguous spread from osteomyelitis or a soft tissue abscess.
Suppurative Arthritis is a subtype of infectious arthritis in which the bacteria seed the joint during episodes of bacteremia. Haemophilus influenzae predominates in children under age 2 years, S. aureus is the main causative agent in older children and adults, and gonococcus is prevalent during late adolescence and young adulthood.
There is sudden onset of pain, redness, and swelling of the joint with fever, leukocytosis, and elevated ESR. In 90% of nongonococcal suppurative arthritis, the infection involves only a single joint-usually the knee. Joint aspiration is typically purulent, and allows identification of the causal agent.
Enterococci
Most common are E. fecalis and E. fecium. Cause inflammation at site of colonization.
Serious resistance to antibiotics. E. fecium is now a vancomycin resistant enterococcus (VRE)
HERPES ZOSTER (Shingles)
An infection with varicella-zoster virus primarily involving the dorsal root ganglia and characterized by vesicular eruption and neuralgic pain in the dermatome of the affected root ganglia.
caused by varicella-zoster virus
Symptoms and Signs
Pain along the site of the future eruption usually precedes the rash by 2 to 3 days. Characteristic crops of vesicles on an erythematous base then appear, following the cutaneous distribution of one or more adjacent dermatomes
Eruptions occur most often in the thoracic or lumbar region and are unilateral. Lesions usually continue to form for about 3 to 5 days
Geniculate zoster (Ramsay Hunt's syndrome) results from involvement of the geniculate ganglion. Pain in the ear and facial paralysis occur on the involved side. A vesicular eruption occurs in the external auditory canal, and taste may be lost in the anterior two thirds of the tongue
Parkinson’s disease
a. Characterized by the degeneration of neurons in the basal ganglia, specifically the substantia nigra and striatum.
b. Histologic findings in affected neurons include Lewy bodies.
c. Clinically, the disease affects involuntary and voluntary movements. Tremors are common. Symptoms include pin-rolling tremors, slowness of movements, muscular rigidity, and shuffling gait.